Partenaires

CNRS


Search


Home > Directory

Bonmatin Jean-Marc

RESEARCH THEME

Scientific works of Jean-Marc Bonmatin are at the interface of chemistry, biology and toxicology. His works mainly focus on 1) measurements of exposures to xenobiotic molecules (especially pesticides acting on the central nervous system), and 2) mechanisms of action of neuro-toxicants, and their effects on living systems. Combination of these two approaches by using a new validated model of eco-toxicological risks, then allows him providing a fine risk assessment, this for both non-target invertebrates, and vertebrates.

Two main classes of insecticides have been extensively studied in the frame of European community research programs: neonicotinoids and phenylpyrazoles. By developing new analytical methods which are the most sensitive so far (LC/GC-MS-MS), JM Bonmatin and co-workers have demonstrated the contamination of pollen and nectar by these insecticides. They also shown that chronic exposure at very low doses induces a significant lethality and a set of sublethal effects, including effects on reproduction.

For a better understanding of these issues at the global level, JM Bonmatin has co-created an international expert group of independent researchers (22 countries): The Task Force on Systemic Pesticides (TFSP). The TFSP has published the first meta-analysis on this subject in 2015, with an update in 2017. The comprehensive meta-analysis revealed that systemic insecticides: a) contaminate significantly all compartments of the environment (soil, water, plants and air), and b) that these insecticides severely impact biodiversity (pollinators, terrestrial and aquatic invertebrates, and insectivorous vertebrates species).

In this context, Jean-Marc Bonmatin is involved in risk assessment of emerging issues, as a member of national expert committees (follow the links: Ministry of agriculture, Institute of bees and pollination, Agency of food safety and environment), as well as for international bodies (follow the links: IUCN, IPBES, OECD, and vice-Chair of the TFSP).

A few more at Washington Post, Cpac Canada, Euractiv,The Guardian, European Commission

Publications

2018   References found : 1

Furlan L., Pozzebon A., Duso C., Simon-Delso N., Sanchez-Bayo F., Marchand P. A., Codato F., Bijleveld van Lexmond M. and Bonmatin J.-M.  (2018)

An update of the Worldwide Integrated Assessment (WIA) on systemic insecticides. Part 3: alternatives to systemic insecticides.

Environmental science and pollution research international, (2018) 148-154.
Over-reliance on pesticides for pest control is inflicting serious damage to the environmental services that underpin agricultural productivity. The widespread use of systemic insecticides, neonicotinoids, and the phenylpyrazole fipronil in particular is assessed here in terms of their actual use in pest management, effects on crop yields, and the development of pest resistance to these compounds in many crops after two decades of usage. Resistance can only be overcome in the longterm by implementing methods that are not exclusively based on synthetic pesticides. A diverse range of pest management tactics is already available, all of which can achieve efficient pest control below the economic injury level while maintaining the productivity of the crops. A novel insurance method against crop failure is shown here as an example of alternative methods that can protect farmer's crops and their livelihoods without having to use insecticides. Finally, some concluding remarks about the need for a new framework for a truly sustainable agriculture that relies mainly on natural ecosystem services instead of chemicals are included; this reinforcing the previous WIA conclusions.

Over-reliance on pesticides for pest control is inflicting serious damage to the environmental services that underpin agricultural productivity. The widespread use of systemic insecticides, neonicotinoids, and the phenylpyrazole fipronil in particular is assessed here in terms of their actual use in pest management, effects on crop yields, and the development of pest resistance to these compounds in many crops after two decades of usage. Resistance can only be overcome in the longterm by implementing methods that are not exclusively based on synthetic pesticides. A diverse range of pest management tactics is already available, all of which can achieve efficient pest control below the economic injury level while maintaining the productivity of the crops. A novel insurance method against crop failure is shown here as an example of alternative methods that can protect farmer’s crops and their livelihoods without having to use insecticides. Finally, some concluding remarks about the need for a new framework for a truly sustainable agriculture that relies mainly on natural ecosystem services instead of chemicals are included; this reinforcing the previous WIA conclusions.


2017   References found : 4

Bonmatin, J-M., Sanchez-Bayo, F., Janairo, J.I.B (Eds)  (2017)

Systemic Pesticides - A Worldwide Assessment

De La Salle University Publishing House (DLSUPH) (2017) Manila (Philippines) 366 pages - ISBN 9789715556484.

Giorio C., Safer A., Sánchez-Bayo F., Tapparo A., Lentola A., Girolami V., van Lexmond M. B. and Bonmatin J.-M.  (2017)

An update of the Worldwide Integrated Assessment (WIA) on systemic insecticides. Part 1: new molecules, metabolism, fate, and transport.

Environmental Science and Pollution Research (2017) p. 1-33.
With the exponential number of published data on neonicotinoids and fipronil during the last decade, an updated review of literature has been conducted in three parts. The present part focuses on gaps of knowledge that have been addressed after publication of the Worldwide Integrated Assessment (WIA) on systemic insecticides in 2015. More specifically, new data on the mode of action and metabolism of neonicotinoids and fipronil, and their toxicity to invertebrates and vertebrates, were obtained. We included the newly detected synergistic effects and/or interactions of these systemic insecticides with other insecticides, fungicides, herbicides, adjuvants, honeybee viruses, and parasites of honeybees. New studies have also investigated the contamination of all environmental compartments (air and dust, soil, water, sediments, and plants) as well as bees and apicultural products, food and beverages, and the exposure of invertebrates and vertebrates to such contaminants. Finally, we review new publications on remediation of neonicotinoids and fipronil, especially in water systems. Conclusions of the previous WIA in 2015 are reinforced; neonicotinoids and fipronil represent a major threat worldwide for biodiversity, ecosystems, and all the services the latter provide.

With the exponential number of published data on neonicotinoids and fipronil during the last decade, an updated review of literature has been conducted in three parts. The present part focuses on gaps of knowledge that have been addressed after publication of the Worldwide Integrated Assessment (WIA) on systemic insecticides in 2015. More specifically, new data on the mode of action and metabolism of neonicotinoids and fipronil, and their toxicity to invertebrates and vertebrates, were obtained. We included the newly detected synergistic effects and/or interactions of these systemic insecticides with other insecticides, fungicides, herbicides, adjuvants, honeybee viruses, and parasites of honeybees. New studies have also investigated the contamination of all environmental compartments (air and dust, soil, water, sediments, and plants) as well as bees and apicultural products, food and beverages, and the exposure of invertebrates and vertebrates to such contaminants. Finally, we review new publications on remediation of neonicotinoids and fipronil, especially in water systems. Conclusions of the previous WIA in 2015 are reinforced; neonicotinoids and fipronil represent a major threat worldwide for biodiversity, ecosystems, and all the services the latter provide.

Pisa L., Goulson D., Yang E.-C., Gibbons D., Sánchez-Bayo F., Mitchell E., Aebi A., van der Sluijs J., MacQuarrie C. J. K., Giorio C., Long E. Y., McField M., Bijleveld van Lexmond M. and Bonmatin J.-M.   (2017)

An update of the Worldwide Integrated Assessment (WIA) on systemic insecticides. Part 2: impacts on organisms and ecosystems.

Environmental Science and Pollution Research, (2017) p. 1-49.
New information on the lethal and sublethal effects of neonicotinoids and fipronil on organisms is presented in this review, complementing the previous Worldwide Integrated Assessment (WIA) in 2015. The high toxicity of these systemic insecticides to invertebrates has been confirmed and expanded to include more species and compounds. Most of the recent research has focused on bees and the sublethal and ecological impacts these insecticides have on pollinators. Toxic effects on other invertebrate taxa also covered predatory and parasitoid natural enemies and aquatic arthropods. Little new information has been gathered on soil organisms. The impact on marine and coastal ecosystems is still largely uncharted. The chronic lethality of neonicotinoids to insects and crustaceans, and the strengthened evidence that these chemicals also impair the immune system and reproduction, highlights the dangers of this particular insecticidal class (neonicotinoids and fipronil), with the potential to greatly decrease populations of arthropods in both terrestrial and aquatic environments. Sublethal effects on fish, reptiles, frogs, birds, and mammals are also reported, showing a better understanding of the mechanisms of toxicity of these insecticides in vertebrates and their deleterious impacts on growth, reproduction, and neurobehaviour of most of the species tested. This review concludes with a summary of impacts on the ecosystem services and functioning, particularly on pollination, soil biota, and aquatic invertebrate communities, thus reinforcing the previous WIA conclusions (van der Sluijs et al. 2015).

New information on the lethal and sublethal effects of neonicotinoids and fipronil on organisms is presented in this review, complementing the previous Worldwide Integrated Assessment (WIA) in 2015. The high toxicity of these systemic insecticides to invertebrates has been confirmed and expanded to include more species and compounds. Most of the recent research has focused on bees and the sublethal and ecological impacts these insecticides have on pollinators. Toxic effects on other invertebrate taxa also covered predatory and parasitoid natural enemies and aquatic arthropods. Little new information has been gathered on soil organisms. The impact on marine and coastal ecosystems is still largely uncharted. The chronic lethality of neonicotinoids to insects and crustaceans, and the strengthened evidence that these chemicals also impair the immune system and reproduction, highlights the dangers of this particular insecticidal class (neonicotinoids and fipronil), with the potential to greatly decrease populations of arthropods in both terrestrial and aquatic environments. Sublethal effects on fish, reptiles, frogs, birds, and mammals are also reported, showing a better understanding of the mechanisms of toxicity of these insecticides in vertebrates and their deleterious impacts on growth, reproduction, and neurobehaviour of most of the species tested. This review concludes with a summary of impacts on the ecosystem services and functioning, particularly on pollination, soil biota, and aquatic invertebrate communities, thus reinforcing the previous WIA conclusions (van der Sluijs et al. 2015).

Sánchez-Bayo, F., Belzunces, L. and Bonmatin, J.-M.  (2017)

Lethal and sublethal effects, and incomplete clearance of ingested imidacloprid in honey bees (Apis mellifera)

Ecotoxicology (2017) 26 (9) 1199-1206
A previous study claimed a differential behavioural resilience between spring or summer honey bees (Apis mellifera) and bumble bees (Bombus terrestris) after exposure to syrup contaminated with 125 µg L−1 imidacloprid for 8 days. The authors of that study based their assertion on the lack of body residues and toxic effects in honey bees, whereas bumble bees showed body residues of imidacloprid and impaired locomotion during the exposure. We have reproduced their experiment using winter honey bees subject to the same protocol. After exposure to syrup contaminated with 125 µg L−1 imidacloprid, honey bees experienced high mortality rates (up to 45%), had body residues of imidacloprid in the range 2.7–5.7 ng g−1 and exhibited abnormal behaviours (restless, apathetic, trembling and falling over) that were significantly different from the controls. There was incomplete clearance of the insecticide during the 10-day exposure period. Our results contrast with the findings reported in the previous study for spring or summer honey bees, but are consistent with the results reported for the other bee species.

A previous study claimed a differential behavioural resilience between spring or summer honey bees (Apis mellifera) and bumble bees (Bombus terrestris) after exposure to syrup contaminated with 125 µg L−1 imidacloprid for 8 days. The authors of that study based their assertion on the lack of body residues and toxic effects in honey bees, whereas bumble bees showed body residues of imidacloprid and impaired locomotion during the exposure. We have reproduced their experiment using winter honey bees subject to the same protocol. After exposure to syrup contaminated with 125 µg L−1 imidacloprid, honey bees experienced high mortality rates (up to 45%), had body residues of imidacloprid in the range 2.7–5.7 ng g−1 and exhibited abnormal behaviours (restless, apathetic, trembling and falling over) that were significantly different from the controls. There was incomplete clearance of the insecticide during the 10-day exposure period. Our results contrast with the findings reported in the previous study for spring or summer honey bees, but are consistent with the results reported for the other bee species.


2015   References found : 9

Nicolle M. et Bonmatin J.-M.  (2015)

Néonicotinoïdes et santé : Les indicateurs vont dans le même sens et doivent nous alerter.

Abeilles & Fleurs (2015) 772, Juin 2015, 24-27.
La Commission du développement durable de l’Assemblée nationale auditionnait plusieurs experts sur l’impact des néonicotinoïdes. Michel Nicolle, médecin, membre de l’association Alerte des médecins sur les pesticides, a exposé l’impact de ces molécules sur la santé humaine. Jean-Marc Bonmatin, chercheur spécialiste des neurotoxiques au CNRS, présentait leurs conséquences sur différentes composantes de l’environnement. Deux exposés captivants... 

Abeilles et Fleurs a souhaité interviewer les deux experts pour qu’ils nous fournissent un éclairage sur cette question peu traitée, ni dans nos colonnes ni ailleurs, celle des risques des néonicotinoïdes pour la santé humaine.

La Commission du développement durable de l’Assemblée nationale auditionnait plusieurs experts sur l’impact des néonicotinoïdes. Michel Nicolle, médecin, membre de l’association Alerte des médecins sur les pesticides, a exposé l’impact de ces molécules sur la santé humaine. Jean-Marc Bonmatin, chercheur spécialiste des neurotoxiques au CNRS, présentait leurs conséquences sur différentes composantes de l’environnement. Deux exposés captivants...
Abeilles et Fleurs a souhaité interviewer les deux experts pour qu’ils nous fournissent un éclairage sur cette question peu traitée, ni dans nos colonnes ni ailleurs, celle des risques des néonicotinoïdes pour la santé humaine.

Bonmatin, J.-M.  (2015)

Co-expositions des abeilles aux facteurs de stress

Rapport d’expertise collective ANSES, Comité d’experts spécialisé Santé animale, Groupe de travail « Co-expositions des abeilles aux facteurs de stress », avril 2015, 252 pages.

Paxton R., Brown M., Kuhlmann M., Goulson D., Decourtye A., Bonmatin J.-M. and Willmer P.  (2015)

Entomology: The bee-all and end-all.

Nature Outlook (2015) 521 (7552) S57-S59.
Seven scientists give their opinions on the biggest challenges faced by bees and bee researchers.

Seven scientists give their opinions on the biggest challenges faced by bees and bee researchers.

Hoppe P. P., Safer A., Amaral-Rogers V., Bonmatin J.-M., Goulson D., Menzel R. and Baer B.  (2015)

Effects of a neonicotinoid pesticide on honey bee colonies: a response to the field study by Pilling et al. (2013)

Environmental Sciences Europe (2015) 27 (28)
Our assessment of the multi-year overwintering study by Pilling et al. (2013) revealed a number of major deficiencies regarding the study design, the protocol and the evaluation of results. Colonies were exposed for short periods per year to flowering oilseed rape and maize grown from thiamethoxam-coated seeds. Thiamethoxam as the sole active ingredient was used, not a more efficacious commercial product, at seed treatment rates that were lower than recommended as per common agricultural practices. Design and adherence to the protocol were described inadequately making it doubtful whether the study was implemented in a traceable way. No results are given for overwintering losses. Much emphasis is laid on presenting condensed raw data but no statistical evaluation is provided. Therefore, the work presented does not contribute new knowledge to our understanding of the potential impact of thiamethoxam products under field conditions. Furthermore, the authors express concern over the refereeing process of the paper. Publications in refereed journals are likely to be taken seriously in political debates and policy-making, and so must be based on truthful data and methodologies.

Our assessment of the multi-year overwintering study by Pilling et al. (2013) revealed a number of major deficiencies regarding the study design, the protocol and the evaluation of results. Colonies were exposed for short periods per year to flowering oilseed rape and maize grown from thiamethoxam-coated seeds. Thiamethoxam as the sole active ingredient was used, not a more efficacious commercial product, at seed treatment rates that were lower than recommended as per common agricultural practices. Design and adherence to the protocol were described inadequately making it doubtful whether the study was implemented in a traceable way. No results are given for overwintering losses. Much emphasis is laid on presenting condensed raw data but no statistical evaluation is provided. Therefore, the work presented does not contribute new knowledge to our understanding of the potential impact of thiamethoxam products under field conditions. Furthermore, the authors express concern over the refereeing process of the paper. Publications in refereed journals are likely to be taken seriously in political debates and policy-making, and so must be based on truthful data and methodologies.

Bonmatin, J.-M., Giorio, C., Girolami, V., Goulson, D., Kreutzweiser, D. P., Krupke, C., Liess, M., Long, E., Marzaro, M., Mitchell, E. A. D., Noome, D. A., Simon-Delso, N. and Tapparo, A.  (2015)

Environmental fate and exposure; neonicotinoids and fipronil

Environmental Science and Pollution Research (2015) 22 (1) 35-67
Systemic insecticides are applied to plants using a wide variety of methods, ranging from foliar sprays to seed treatments and soil drenches. Neonicotinoids and fipronil are among the most widely used pesticides in the world. Their popularity is largely due to their high toxicity to invertebrates, the ease and flexibility with which they can be applied, their long persistence, and their systemic nature, which ensures that they spread to all parts of the target crop. However, these properties also increase the probability of environmental contamination and exposure of nontarget organisms. Environmental contamination occurs via a number of routes including dust generated during drilling of dressed seeds, contamination and accumulation in arable soils and soil water, runoff into waterways, and uptake of pesticides by nontarget plants via their roots or dust deposition on leaves. Persistence in soils, waterways, and nontarget plants is variable but can be prolonged; for example, the half-lives of neonicotinoids in soils can exceed 1,000 days, so they can accumulate when used repeatedly. Similarly, they can persist in woody plants for periods exceeding 1 year. Breakdown results in toxic metabolites, though concentrations of these in the environment are rarely measured. Overall, there is strong evidence that soils, waterways, and plants in agricultural environments and neighboring areas are contaminated with variable levels of neonicotinoids or fipronil mixtures and their metabolites (soil, parts per billion (ppb)-parts per million (ppm) range; water, parts per trillion (ppt)-ppb range; and plants, ppb-ppm range). This provides multiple routes for chronic (and acute in some cases) exposure of nontarget animals. For example, pollinators are exposed through direct contact with dust during drilling; consumption of pollen, nectar, or guttation drops from seed-treated crops, water, and consumption of contaminated pollen and nectar from wild flowers and trees growing near-treated crops. Studies of food stores in honeybee colonies from across the globe demonstrate that colonies are routinely and chronically exposed to neonicotinoids, fipronil, and their metabolites (generally in the 1–100 ppb range), mixed with other pesticides some of which are known to act synergistically with neonicotinoids. Other nontarget organisms, particularly those inhabiting soils, aquatic habitats, or herbivorous insects feeding on noncrop plants in farmland, will also inevitably receive exposure, although data are generally lacking for these groups. We summarize the current state of knowledge regarding the environmental fate of these compounds by outlining what is known about the chemical properties of these compounds, and placing these properties in the context of modern agricultural practices.

Systemic insecticides are applied to plants using a wide variety of methods, ranging from foliar sprays to seed treatments and soil drenches. Neonicotinoids and fipronil are among the most widely used pesticides in the world. Their popularity is largely due to their high toxicity to invertebrates, the ease and flexibility with which they can be applied, their long persistence, and their systemic nature, which ensures that they spread to all parts of the target crop. However, these properties also increase the probability of environmental contamination and exposure of nontarget organisms. Environmental contamination occurs via a number of routes including dust generated during drilling of dressed seeds, contamination and accumulation in arable soils and soil water, runoff into waterways, and uptake of pesticides by nontarget plants via their roots or dust deposition on leaves. Persistence in soils, waterways, and nontarget plants is variable but can be prolonged; for example, the half-lives of neonicotinoids in soils can exceed 1,000 days, so they can accumulate when used repeatedly. Similarly, they can persist in woody plants for periods exceeding 1 year. Breakdown results in toxic metabolites, though concentrations of these in the environment are rarely measured. Overall, there is strong evidence that soils, waterways, and plants in agricultural environments and neighboring areas are contaminated with variable levels of neonicotinoids or fipronil mixtures and their metabolites (soil, parts per billion (ppb)-parts per million (ppm) range; water, parts per trillion (ppt)-ppb range; and plants, ppb-ppm range). This provides multiple routes for chronic (and acute in some cases) exposure of nontarget animals. For example, pollinators are exposed through direct contact with dust during drilling; consumption of pollen, nectar, or guttation drops from seed-treated crops, water, and consumption of contaminated pollen and nectar from wild flowers and trees growing near-treated crops. Studies of food stores in honeybee colonies from across the globe demonstrate that colonies are routinely and chronically exposed to neonicotinoids, fipronil, and their metabolites (generally in the 1–100 ppb range), mixed with other pesticides some of which are known to act synergistically with neonicotinoids. Other nontarget organisms, particularly those inhabiting soils, aquatic habitats, or herbivorous insects feeding on noncrop plants in farmland, will also inevitably receive exposure, although data are generally lacking for these groups. We summarize the current state of knowledge regarding the environmental fate of these compounds by outlining what is known about the chemical properties of these compounds, and placing these properties in the context of modern agricultural practices.

van der Sluijs, J. P. Amaral-Rogers, V. Belzunces, L. P. Bijleveld van Lexmond, M. F. I. J. Bonmatin, J. M. Chagnon, M. Downs, C. A. Furlan, L. Gibbons, D. W. Giorio, C. Girolami, V. Goulson, D. Kreutzweiser, D. P. Krupke, C. Liess, M. Long, E. McField, M. Mineau, P. Mitchell, E. A. D. Morrissey, C. A. Noome, D. A. Pisa, L. Settele, J. Simon-Delso, N. Stark, J. D. Tapparo, A. Van Dyck, H. van Praagh, J. Whitehorn, P. R. Wiemers, M.  (2015)

Conclusions of the Worldwide Integrated Assessment on the risks of neonicotinoids and fipronil to biodiversity and ecosystem functioning

Environmental Science and Pollution Research (2015) 22 (1) 148-154
The side effects of the current global use of pesticides on wildlife, particularly at higher levels of biological organization: populations, communities and ecosystems, are poorly understood (Köhler and Triebskorn 2013). Here, we focus on one of the problematic groups of agrochemicals, the systemic insecticides fipronil and those of the neonicotinoid family. The increasing global reliance on the partly prophylactic use of these persistent and potent neurotoxic systemic insecticides has raised concerns about their impacts on biodiversity, ecosystem functioning and ecosystem services provided by a wide range of affected species and environments. The present scale of use, combined with the properties of these compounds, has resulted in widespread contamination of agricultural soils, freshwater resources, wetlands, non-target vegetation and estuarine and coastal marine systems, which means that many organisms inhabiting these habitats are being repeatedly and chronically expose.

The side effects of the current global use of pesticides on wildlife, particularly at higher levels of biological organization: populations, communities and ecosystems, are poorly understood (Köhler and Triebskorn 2013). Here, we focus on one of the problematic groups of agrochemicals, the systemic insecticides fipronil and those of the neonicotinoid family. The increasing global reliance on the partly prophylactic use of these persistent and potent neurotoxic systemic insecticides has raised concerns about their impacts on biodiversity, ecosystem functioning and ecosystem services provided by a wide range of affected species and environments. The present scale of use, combined with the properties of these compounds, has resulted in widespread contamination of agricultural soils, freshwater resources, wetlands, non-target vegetation and estuarine and coastal marine systems, which means that many organisms inhabiting these habitats are being repeatedly and chronically expose.

Simon-Delso, N. Amaral-Rogers, V. Belzunces, L. P. Bonmatin, J. M. Chagnon, M. Downs, C. Furlan, L. Gibbons, D. W. Giorio, C. Girolami, V. Goulson, D. Kreutzweiser, D. P. Krupke, C. H. Liess, M. Long, E. McField, M. Mineau, P. Mitchell, E. A. D. Morrissey, C. A. Noome, D. Pisa, L., Settele, J., Stark, J.D., Tapparo, A., Van Dyck, H., Van Praagh, J., Van der Sluijs, J.P., Whitehorn, P.R. and Wiemers, M.  (2015)

Systemic insecticides (neonicotinoids and fipronil): trends, uses, mode of action and metabolites

Environmental Science and Pollution Research (2015) 22 (1) 5-34
Since their discovery in the late 1980s, neonicotinoid pesticides have become the most widely used class of insecticides worldwide, with large-scale applications ranging from plant protection (crops, vegetables, fruits), veterinary products, and biocides to invertebrate pest control in fish farming. In this review, we address the phenyl-pyrazole fipronil together with neonicotinoids because of similarities in their toxicity, physicochemical profiles, and presence in the environment. Neonicotinoids and fipronil currently account for approximately one third of the world insecticide market; the annual world production of the archetype neonicotinoid, imidacloprid, was estimated to be ca. 20,000 tonnes active substance in 2010. There were several reasons for the initial success of neonicotinoids and fipronil: (1) there was no known pesticide resistance in target pests, mainly because of their recent development, (2) their physicochemical properties included many advantages over previous generations of insecticides (i.e., organophosphates, carbamates, pyrethroids, etc.), and (3) they shared an assumed reduced operator and consumer risk. Due to their systemic nature, they are taken up by the roots or leaves and translocated to all parts of the plant, which, in turn, makes them effectively toxic to herbivorous insects. The toxicity persists for a variable period of time—depending on the plant, its growth stage, and the amount of pesticide applied. A wide variety of applications are available, including the most common prophylactic non-Good Agricultural Practices (GAP) application by seed coating. As a result of their extensive use and physicochemical properties, these substances can be found in all environmental compartments including soil, water, and air. Neonicotinoids and fipronil operate by disrupting neural transmission in the central nervous system of invertebrates. Neonicotinoids mimic the action of neurotransmitters, while fipronil inhibits neuronal receptors. In doing so, they continuously stimulate neurons leading ultimately to death of target invertebrates. Like virtually all insecticides, they can also have lethal and sublethal impacts on non-target organisms, including insect predators and vertebrates. Furthermore, a range of synergistic effects with other stressors have been documented. Here, we review extensively their metabolic pathways, showing how they form both compound-specific and common metabolites which can themselves be toxic. These may result in prolonged toxicity. Considering their wide commercial expansion, mode of action, the systemic properties in plants, persistence and environmental fate, coupled with limited information about the toxicity profiles of these compounds and their metabolites, neonicotinoids and fipronil may entail significant risks to the environment. A global evaluation of the potential collateral effects of their use is therefore timely. The present paper and subsequent chapters in this review of the global literature explore these risks and show a growing body of evidence that persistent, low concentrations of these insecticides pose serious risks of undesirable environmental impacts.

Since their discovery in the late 1980s, neonicotinoid pesticides have become the most widely used class of insecticides worldwide, with large-scale applications ranging from plant protection (crops, vegetables, fruits), veterinary products, and biocides to invertebrate pest control in fish farming. In this review, we address the phenyl-pyrazole fipronil together with neonicotinoids because of similarities in their toxicity, physicochemical profiles, and presence in the environment. Neonicotinoids and fipronil currently account for approximately one third of the world insecticide market; the annual world production of the archetype neonicotinoid, imidacloprid, was estimated to be ca. 20,000 tonnes active substance in 2010. There were several reasons for the initial success of neonicotinoids and fipronil: (1) there was no known pesticide resistance in target pests, mainly because of their recent development, (2) their physicochemical properties included many advantages over previous generations of insecticides (i.e., organophosphates, carbamates, pyrethroids, etc.), and (3) they shared an assumed reduced operator and consumer risk. Due to their systemic nature, they are taken up by the roots or leaves and translocated to all parts of the plant, which, in turn, makes them effectively toxic to herbivorous insects. The toxicity persists for a variable period of time—depending on the plant, its growth stage, and the amount of pesticide applied. A wide variety of applications are available, including the most common prophylactic non-Good Agricultural Practices (GAP) application by seed coating. As a result of their extensive use and physicochemical properties, these substances can be found in all environmental compartments including soil, water, and air. Neonicotinoids and fipronil operate by disrupting neural transmission in the central nervous system of invertebrates. Neonicotinoids mimic the action of neurotransmitters, while fipronil inhibits neuronal receptors. In doing so, they continuously stimulate neurons leading ultimately to death of target invertebrates. Like virtually all insecticides, they can also have lethal and sublethal impacts on non-target organisms, including insect predators and vertebrates. Furthermore, a range of synergistic effects with other stressors have been documented. Here, we review extensively their metabolic pathways, showing how they form both compound-specific and common metabolites which can themselves be toxic. These may result in prolonged toxicity. Considering their wide commercial expansion, mode of action, the systemic properties in plants, persistence and environmental fate, coupled with limited information about the toxicity profiles of these compounds and their metabolites, neonicotinoids and fipronil may entail significant risks to the environment. A global evaluation of the potential collateral effects of their use is therefore timely. The present paper and subsequent chapters in this review of the global literature explore these risks and show a growing body of evidence that persistent, low concentrations of these insecticides pose serious risks of undesirable environmental impacts.

Pisa, L.W., Amaral-Rogers, V., Belzunces, L.P., Bonmatin, J.M., Downs, C.A., Goulson, D., Kreutzweiser, D.P., Krupke, C., Liess, M., McField, M., Morrissey, C.A., Noome, D.A., Settele, J., Simon-Delso, N., Stark, J.D., Van der Sluijs, J.P., Van Dyck, H. and Wiemers, M.  (2015)

Effects of neonicotinoids and fipronil on non-target invertebrates

Environmental Science and Pollution Research (2015) 22 (1) 68-102
We assessed the state of knowledge regarding the effects of large-scale pollution with neonicotinoid insecticides and fipronil on non-target invertebrate species of terrestrial, freshwater and marine environments. A large section of the assessment is dedicated to the state of knowledge on sublethal effects on honeybees (Apis mellifera) because this important pollinator is the most studied non-target invertebrate species. Lepidoptera (butterflies and moths), Lumbricidae (earthworms), Apoidae sensu lato (bumblebees, solitary bees) and the section “other invertebrates” review available studies on the other terrestrial species. The sections on freshwater and marine species are rather short as little is known so far about the impact of neonicotinoid insecticides and fipronil on the diverse invertebrate fauna of these widely exposed habitats. For terrestrial and aquatic invertebrate species, the known effects of neonicotinoid pesticides and fipronil are described ranging from organismal toxicology and behavioural effects to population-level effects. For earthworms, freshwater and marine species, the relation of findings to regulatory risk assessment is described. Neonicotinoid insecticides exhibit very high toxicity to a wide range of invertebrates, particularly insects, and field-realistic exposure is likely to result in both lethal and a broad range of important sublethal impacts. There is a major knowledge gap regarding impacts on the grand majority of invertebrates, many of which perform essential roles enabling healthy ecosystem functioning. The data on the few non-target species on which field tests have been performed are limited by major flaws in the outdated test protocols. Despite large knowledge gaps and uncertainties, enough knowledge exists to conclude that existing levels of pollution with neonicotinoids and fipronil resulting from presently authorized uses frequently exceed the lowest observed adverse effect concentrations and are thus likely to have large-scale and wide ranging negative biological and ecological impacts on a wide range of non-target invertebrates in terrestrial, aquatic, marine and benthic habitats.

We assessed the state of knowledge regarding the effects of large-scale pollution with neonicotinoid insecticides and fipronil on non-target invertebrate species of terrestrial, freshwater and marine environments. A large section of the assessment is dedicated to the state of knowledge on sublethal effects on honeybees (Apis mellifera) because this important pollinator is the most studied non-target invertebrate species. Lepidoptera (butterflies and moths), Lumbricidae (earthworms), Apoidae sensu lato (bumblebees, solitary bees) and the section “other invertebrates” review available studies on the other terrestrial species. The sections on freshwater and marine species are rather short as little is known so far about the impact of neonicotinoid insecticides and fipronil on the diverse invertebrate fauna of these widely exposed habitats. For terrestrial and aquatic invertebrate species, the known effects of neonicotinoid pesticides and fipronil are described ranging from organismal toxicology and behavioural effects to population-level effects. For earthworms, freshwater and marine species, the relation of findings to regulatory risk assessment is described. Neonicotinoid insecticides exhibit very high toxicity to a wide range of invertebrates, particularly insects, and field-realistic exposure is likely to result in both lethal and a broad range of important sublethal impacts. There is a major knowledge gap regarding impacts on the grand majority of invertebrates, many of which perform essential roles enabling healthy ecosystem functioning. The data on the few non-target species on which field tests have been performed are limited by major flaws in the outdated test protocols. Despite large knowledge gaps and uncertainties, enough knowledge exists to conclude that existing levels of pollution with neonicotinoids and fipronil resulting from presently authorized uses frequently exceed the lowest observed adverse effect concentrations and are thus likely to have large-scale and wide ranging negative biological and ecological impacts on a wide range of non-target invertebrates in terrestrial, aquatic, marine and benthic habitats.

van Lexmond, M., Bonmatin, J.-M., Goulson, D., Noome, D.A.  (2015)

Worldwide integrated assessment on systemic pesticides.

Environmental Science and Pollution Research (2015) 22 (1) 1-4


2014   References found : 4

Katouzian-Safadi M. and Bonmatin J.-M.  (2014)

Du diagnostic differential aux therapies prudentes: Le traité de la rougeole et de la variole de Râzî (From differential diagnosis to caution treatments, Treatise of Smallpox and measles of al-Râzî)

In "Medicine and healing in the ancient Mediterranean World", Michaelides D. Ed., Oxbow Books (2014) 332-3343
There are many recoverable aspects and indications concerning medicine and healing in the ancient past – from the archaeological evidence of skeletal remains, grave-goods comprising medical and/or surgical equipment and visual representations in tombs and other monuments thorough to epigraphic and literary sources. The 42 papers presented here cover many aspects medicine in the Mediterranean world during Antiquity and early Byzantine times, bringing together both internationally established specialists on the history of medicine and researchers in the early stages of their career. 

The contributions are grouped under a series of headings: medicine and archaeology; media (online access to electronic corpus); the Aegean; medical authors/schools of medicine; surgery; medicaments and cures; skeletal remains; new research in Cyprus; Asklepios and incubation; and Byzantine, Arab and medieval sources. These subject areas are addressed through a combination of wide ranging archaeological and osteological data and the examination and interpretation of philosophical, literary and historiographical texts to provide a comprehensive suite of studies into early practices in this fundamental field of human experience.

There are many recoverable aspects and indications concerning medicine and healing in the ancient past – from the archaeological evidence of skeletal remains, grave-goods comprising medical and/or surgical equipment and visual representations in tombs and other monuments thorough to epigraphic and literary sources. The 42 papers presented here cover many aspects medicine in the Mediterranean world during Antiquity and early Byzantine times, bringing together both internationally established specialists on the history of medicine and researchers in the early stages of their career.

The contributions are grouped under a series of headings: medicine and archaeology; media (online access to electronic corpus); the Aegean; medical authors/schools of medicine; surgery; medicaments and cures; skeletal remains; new research in Cyprus; Asklepios and incubation; and Byzantine, Arab and medieval sources. These subject areas are addressed through a combination of wide ranging archaeological and osteological data and the examination and interpretation of philosophical, literary and historiographical texts to provide a comprehensive suite of studies into early practices in this fundamental field of human experience.

Bonmatin, J.M.  (2014)

Die Neonicotinoide gelangten auf Grund falscher Annahmen auf den Markt

OEKOSKOP (2014),1 (14) 9-12

Charpentier, G. Louat, F. Bonmatin, J. M. Marchand, P. A. Vanier, F. Locker, D. Decoville, M.  (2014)

Lethal and sublethal effects of imidacloprid, after chronic exposure, on the insect model Drosophila melanogaster

Environmental science and technology (2014) 48 (7) 4096-4102
Neonicotinoids are subjected to vigilance because of environmental contaminations and deleterious effects on bees. Imidacloprid (IMI) is one of the most representative insecticides of this family. At chronic exposure, concentration-effect relationships are non linear. An insect model should allow a better description of this toxicity. We compared the lethal concentration 50% (LC50) of IMI for a Drosophila-field strain, after acute and chronic exposure. Relative to the acute LC50, the chronic LC50 was lowered by a factor of 29 for males (1.3 mM/45 muM), 52 for larvae (157 muM/3 muM) and more than 172 for females (>3.1 mM/18 muM). Chronic exposure also revealed significant lethal and sublethal effects, at concentrations 3-5 orders of magnitude lower than the chronic LC50. Mean mortalities reached 28% (at 3.91 nM) and 27% (at 39.1 nM) for females and males, respectively. Fecundity decreased of 16% at 1.96 nM. Mating increased of 30% at 0.391 nM. The LOEC (lowest observed effect concentration: 0.391 nM) was 46 000 times lower than the chronic LC50 for males; it was 115 000 times lower than the chronic LC50 for females. This study illuminates effects that neonicotinoids can induce at very low concentrations. This is of particular interest for nontarget insects and for insect dependent species.

Neonicotinoids are subjected to vigilance because of environmental contaminations and deleterious effects on bees. Imidacloprid (IMI) is one of the most representative insecticides of this family. At chronic exposure, concentration-effect relationships are non linear. An insect model should allow a better description of this toxicity. We compared the lethal concentration 50% (LC50) of IMI for a Drosophila-field strain, after acute and chronic exposure. Relative to the acute LC50, the chronic LC50 was lowered by a factor of 29 for males (1.3 mM/45 muM), 52 for larvae (157 muM/3 muM) and more than 172 for females (>3.1 mM/18 muM). Chronic exposure also revealed significant lethal and sublethal effects, at concentrations 3-5 orders of magnitude lower than the chronic LC50. Mean mortalities reached 28% (at 3.91 nM) and 27% (at 39.1 nM) for females and males, respectively. Fecundity decreased of 16% at 1.96 nM. Mating increased of 30% at 0.391 nM. The LOEC (lowest observed effect concentration: 0.391 nM) was 46 000 times lower than the chronic LC50 for males; it was 115 000 times lower than the chronic LC50 for females. This study illuminates effects that neonicotinoids can induce at very low concentrations. This is of particular interest for nontarget insects and for insect dependent species.

Paradis D., Berail G., Bonmatin J.M. and Belzunces L.P.  (2014)

Sensitive analytical methods for 22 relevant insecticides of 3 chemical families in honey by GC-MS/MS and LC-MS/MS

Analytical and bioanalytical chemistry (2014) 406 (2) 621-633
Several methods for analyzing pesticides in honey have been developed. However, they do not always reach the sufficiently low limits of quantification (LOQ) needed to quantify pesticides toxic to honey bees at low doses. To properly evaluate the toxicity of pesticides, LOQ have to reach at least 1 ng/g. In this context, we developed extraction and analytical methods for the simultaneous detection of 22 relevant insecticides belonging to three chemical families (neonicotinoids, pyrethroids, and pyrazoles) in honey. The insecticides were extracted with the QuEChERS method that consists in an extraction and a purification with mixtures of salts adapted to the matrix and the substances to be extracted. Analyses were performed by gas chromatography coupled with tandem mass spectrometry (GC-MS/MS) for the pyrazoles and the pyrethroids and by high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS) for the neonicotinoids and ethiprole. Calibration curves were built from various honey types fortified at different concentrations. Linear responses were obtained between 0.2 and 5 ng/g. Limits of detection (LOD) ranged between 0.07 and 0.2 ng/g, and LOQ ranged between 0.2 and 0.5 ng/g. The mean extraction yields ranged between 63 % and 139 % with RSD <25 %. A complete validation of the methods also examined recovery rates and specificity. These methods were applied to 90 honey samples collected during a 2009-2010 field study in two apiaries placed in different anthropic contexts.

Several methods for analyzing pesticides in honey have been developed. However, they do not always reach the sufficiently low limits of quantification (LOQ) needed to quantify pesticides toxic to honey bees at low doses. To properly evaluate the toxicity of pesticides, LOQ have to reach at least 1 ng/g. In this context, we developed extraction and analytical methods for the simultaneous detection of 22 relevant insecticides belonging to three chemical families (neonicotinoids, pyrethroids, and pyrazoles) in honey. The insecticides were extracted with the QuEChERS method that consists in an extraction and a purification with mixtures of salts adapted to the matrix and the substances to be extracted. Analyses were performed by gas chromatography coupled with tandem mass spectrometry (GC-MS/MS) for the pyrazoles and the pyrethroids and by high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS) for the neonicotinoids and ethiprole. Calibration curves were built from various honey types fortified at different concentrations. Linear responses were obtained between 0.2 and 5 ng/g. Limits of detection (LOD) ranged between 0.07 and 0.2 ng/g, and LOQ ranged between 0.2 and 0.5 ng/g. The mean extraction yields ranged between 63 % and 139 % with RSD <25 %. A complete validation of the methods also examined recovery rates and specificity. These methods were applied to 90 honey samples collected during a 2009-2010 field study in two apiaries placed in different anthropic contexts.


2013   References found : 2

Bonmatin J.-M  (2013)

Contamination de la ruche : l’exemple révélateur des insecticides systémiques dans les plantes, les pollens, les nectars et les abeilles

Colloque "L’abeille, indicateur des écosystèmes", Bruxelles (2013) 23-28.

van der Sluijs, J. P,. Simon-Delso, N., Goulson, D., Maxim, L., Bonmatin, J.-M. and Belzunces, L. P.  (2013)

Neonicotinoids, bee disorders and the sustainability of pollinator services

Current Opinion in Environmental Sustainability (2013) 5 (3-4) 293-305
In less than 20 years, neonicotinoids have become the most widely used class of insecticides with a global market share of more than 25%. For pollinators, this has transformed the agrochemical landscape. These chemicals mimic the acetylcholine neurotransmitter and are highly neurotoxic to insects. Their systemic mode of action inside plants means phloemic and xylemic transport that results in translocation to pollen and nectar. Their wide application, persistence in soil and water and potential for uptake by succeeding crops and wild plants make neonicotinoids bioavailable to pollinators at sublethal concentrations for most of the year. This results in the frequent presence of neonicotinoids in honeybee hives. At field realistic doses, neonicotinoids cause a wide range of adverse sublethal effects in honeybee and bumblebee colonies, affecting colony performance through impairment of foraging success, brood and larval development, memory and learning, damage to the central nervous system, susceptibility to diseases, hive hygiene etc. Neonicotinoids exhibit a toxicity that can be amplified by various other agrochemicals and they synergistically reinforce infectious agents such as Nosema ceranae which together can produce colony collapse. The limited available data suggest that they are likely to exhibit similar toxicity to virtually all other wild insect pollinators. The worldwide production of neonicotinoids is still increasing. Therefore a transition to pollinator-friendly alternatives to neonicotinoids is urgently needed for the sake of the sustainability of pollinator ecosystem services.

In less than 20 years, neonicotinoids have become the most widely used class of insecticides with a global market share of more than 25%. For pollinators, this has transformed the agrochemical landscape. These chemicals mimic the acetylcholine neurotransmitter and are highly neurotoxic to insects. Their systemic mode of action inside plants means phloemic and xylemic transport that results in translocation to pollen and nectar. Their wide application, persistence in soil and water and potential for uptake by succeeding crops and wild plants make neonicotinoids bioavailable to pollinators at sublethal concentrations for most of the year. This results in the frequent presence of neonicotinoids in honeybee hives. At field realistic doses, neonicotinoids cause a wide range of adverse sublethal effects in honeybee and bumblebee colonies, affecting colony performance through impairment of foraging success, brood and larval development, memory and learning, damage to the central nervous system, susceptibility to diseases, hive hygiene etc. Neonicotinoids exhibit a toxicity that can be amplified by various other agrochemicals and they synergistically reinforce infectious agents such as Nosema ceranae which together can produce colony collapse. The limited available data suggest that they are likely to exhibit similar toxicity to virtually all other wild insect pollinators. The worldwide production of neonicotinoids is still increasing. Therefore a transition to pollinator-friendly alternatives to neonicotinoids is urgently needed for the sake of the sustainability of pollinator ecosystem services.


2012   References found : 1

Bonmatin J.-M. et Marchand P. A.  (2012)

Two very sensitive HPLC-MS-MS methods to detect nicotinoid pesticides in pollen and in bee. [Deux méthodes HPLC-MS-MS très sensibles pour détecter les pesticides nicotinoïdes dans les pollens et les abeilles]

Journée Scientifique Apicole, Oniris, Nantes. Lambert O., L’Hostis M. et Barbanson J.-M. Ed., (2012) 74-82.
Several factors are suspected to participate to the weakening of honeybee's worldwide (varroa, pesticides, pathogens and poor diversity of food resources being the major ones). Among pesticides, nicotinoid insecticides form the class of the most toxic compounds to bees; considering lethal, sub-lethal and chronic effects. Knowledge of bee exposure is then required. Sensitive detection of thiamethoxam, clothianidin imidacloprid, acetamiprid and thiacloprid was performed for pollen by HPLC-MS-MS. Limits of detection were ranging from 0.002 to 0.2 ng/g while the limit of quantification was set uniformly at 1 ng/g. Sensitive detection of these 5 nicotinoids was also developed in bees by HPLC-MS-MS. Here, LOD's ranged from 0.02 to 0.3 ng/g with a LOQ uniformly set at 0.5 ng/g. Quality parameters permitted validation of both methods in terms of selectivity, recovery rates, linearity, accuracy etc. Both methods were applied to samples from fields. The first method allowed describing the contamination of pollen in contact with foragers and entering in the beehive. The second method allowed verifying the presence of nicotinoids in dead bees, when sampling conditions were favorable (before toxicants were metabolized or degraded). 

Français :

Plusieurs facteurs sont suspectés de participer à l’affaiblissement des colonies d’abeilles à travers le Monde (varroas, pesticides, agents pathogènes et la faible diversité des sources de nourriture étant les principaux facteurs). Parmi les pesticides, les insecticides nicotinoïdes composent la classe des substances les plus toxiques pour les abeilles, en considérant leurs effets sublétaux et chroniques. La connaissance de l’exposition des abeilles est donc requise.

La détection sensible du thiamethoxam, chlothianidine imidaclopride, acétamipride et thiaclopride a été mise au point dans les pollens par HPLC-MS-MS. Les limites de détection sont dans la gamme de 0,002 à 0,2 ng/g, tandis que la limite de quantification a été fixée à 1 ng/g. La détection sensible de ces 5 nicotinoïdes a également été développée pour les abeilles par HPLC-MS-MS. Ici les LODs vont de 0,02 à 0,3 ng/g et la LOQ est uniforme à 0,5 ng/g. Les méthodes sont validées sur la base des critères de qualité en termes de sélectivité, taux de recouvrement, linéarité, précision, etc.

Les deux méthodes ont été utilisées pour analyser des échantillons de pleins champs. La première méthode a permis de décrire la contamination des pollens en contact avec les butineuses et entrant dans la ruche. La seconde méthode a permis de vérifier la présence de nicotinoïdes dans les abeilles mortes lorsque les conditions de prélèvement étaient favorables (c.à.d. avant que les toxiques ne soient métabolisés ou dégradés).

Several factors are suspected to participate to the weakening of honeybee’s worldwide (varroa, pesticides, pathogens and poor diversity of food resources being the major ones). Among pesticides, nicotinoid insecticides form the class of the most toxic compounds to bees; considering lethal, sub-lethal and chronic effects. Knowledge of bee exposure is then required. Sensitive detection of thiamethoxam, clothianidin imidacloprid, acetamiprid and thiacloprid was performed for pollen by HPLC-MS-MS. Limits of detection were ranging from 0.002 to 0.2 ng/g while the limit of quantification was set uniformly at 1 ng/g. Sensitive detection of these 5 nicotinoids was also developed in bees by HPLC-MS-MS. Here, LOD’s ranged from 0.02 to 0.3 ng/g with a LOQ uniformly set at 0.5 ng/g. Quality parameters permitted validation of both methods in terms of selectivity, recovery rates, linearity, accuracy etc. Both methods were applied to samples from fields. The first method allowed describing the contamination of pollen in contact with foragers and entering in the beehive. The second method allowed verifying the presence of nicotinoids in dead bees, when sampling conditions were favorable (before toxicants were metabolized or degraded).

Français :
Plusieurs facteurs sont suspectés de participer à l’affaiblissement des colonies d’abeilles à travers le Monde (varroas, pesticides, agents pathogènes et la faible diversité des sources de nourriture étant les principaux facteurs). Parmi les pesticides, les insecticides nicotinoïdes composent la classe des substances les plus toxiques pour les abeilles, en considérant leurs effets sublétaux et chroniques. La connaissance de l’exposition des abeilles est donc requise.
La détection sensible du thiamethoxam, chlothianidine imidaclopride, acétamipride et thiaclopride a été mise au point dans les pollens par HPLC-MS-MS. Les limites de détection sont dans la gamme de 0,002 à 0,2 ng/g, tandis que la limite de quantification a été fixée à 1 ng/g. La détection sensible de ces 5 nicotinoïdes a également été développée pour les abeilles par HPLC-MS-MS. Ici les LODs vont de 0,02 à 0,3 ng/g et la LOQ est uniforme à 0,5 ng/g. Les méthodes sont validées sur la base des critères de qualité en termes de sélectivité, taux de recouvrement, linéarité, précision, etc.
Les deux méthodes ont été utilisées pour analyser des échantillons de pleins champs. La première méthode a permis de décrire la contamination des pollens en contact avec les butineuses et entrant dans la ruche. La seconde méthode a permis de vérifier la présence de nicotinoïdes dans les abeilles mortes lorsque les conditions de prélèvement étaient favorables (c.à.d. avant que les toxiques ne soient métabolisés ou dégradés).


2011   References found : 1

Katouzian-Safadi M. et Bonmatin J.-M.  (2011)

Râzî et le traitement de la bile noire par les hieras, Sciences et philosophie arabes : méthode, problème et cas.

Actes du Congrès international de la SIHSPAI, Carthage, Tunisie, Bayt al-Hikma Ed. (2011) 12 pages.


2010   References found : 2

Bonmatin J.-M.   (2010)

Exposición de abejas a plaguicidas

Vida apicola (2010) n°159

Colin M. E., Bonmatin J.-M., Marchand P. A. etBelzunces L. P.  (2010)

Postulats de toxicologie environnementale.

Journée Scientifiques Apicoles, Oniris (2010) 59-62.


2007   References found : 2

Bonmatin J.-M., Marchand P. A., Cotte J.-F., Aajoud A., Casabianca H., Goutailler G., Courtiade M.  (2007)

Bees and systemic insecticides (imidacloprid, fipronil) in pollen: subnano-quantification by HPLC/MS/MS and GC/MS.

In "Environmental Fate and Ecological Effects of Pesticide" (Del Re AA., Capri M., Fragoulis E., Trevisan M.), Eds. La Goliardica Pavese, Pavia, (Italie) (2007) 827-824.
Imidacloprid and fipronil are two insecticides acting on the central nervous system. They are used worldwide, from the mid nineties, especially for seed coating of crops. Concomitantly to their introduction and their increasing use in French fields, honeybee populations decreased. Bee problems are nowadays reported in other countries (also called disappearing disease, desplobación de las colmenas, trouble des abeilles, deperimento degli apiari or colony collapse disorder). Bee problems have certainly several origins. Contamination of pollen and nectar by such chemicals appeared as one of the most probable cause, since subletal effects and chronic intoxications were observed on bees, at very low concentrations. We developed fully validated methods to measure contamination in pollen (sunflower and maize) for imidacloprid (HPLC/MS/MS) and for fipronil and 3 of its derivatives (GC/MS). For imidacloprid LOD and LOQ are 0.3 and 1 ng/g, respectively. For fipronil and each derivative (fiprole), LOD and LOQ are 0.07 and 0.2 ng/g, respectively. The averaged level of imidacloprid in pollen was 2-3 ng/g, which is 20-30 times higher than the concentration inducing significant mortality by chronic intoxication. Fiproles were detected in 48% of pollens issuing from treated crops. Fipronil and its sulfone derivative represented 77% and 17% of contaminants, respectively. The averaged fiprole sum Σf was 0.3 - 0.4 ng/g, which is 30-40 times higher than the concentration inducing significant mortality of bees by chronic intoxication.

Imidacloprid and fipronil are two insecticides acting on the central nervous system. They are used worldwide, from the mid nineties, especially for seed coating of crops. Concomitantly to their introduction and their increasing use in French fields, honeybee populations decreased. Bee problems are nowadays reported in other countries (also called disappearing disease, desplobación de las colmenas, trouble des abeilles, deperimento degli apiari or colony collapse disorder). Bee problems have certainly several origins. Contamination of pollen and nectar by such chemicals appeared as one of the most probable cause, since subletal effects and chronic intoxications were observed on bees, at very low concentrations. We developed fully validated methods to measure contamination in pollen (sunflower and maize) for imidacloprid (HPLC/MS/MS) and for fipronil and 3 of its derivatives (GC/MS). For imidacloprid LOD and LOQ are 0.3 and 1 ng/g, respectively. For fipronil and each derivative (fiprole), LOD and LOQ are 0.07 and 0.2 ng/g, respectively. The averaged level of imidacloprid in pollen was 2-3 ng/g, which is 20-30 times higher than the concentration inducing significant mortality by chronic intoxication. Fiproles were detected in 48% of pollens issuing from treated crops. Fipronil and its sulfone derivative represented 77% and 17% of contaminants, respectively. The averaged fiprole sum Σf was 0.3 - 0.4 ng/g, which is 30-40 times higher than the concentration inducing significant mortality of bees by chronic intoxication.

Zhang, QS; Ongus, JR; Boot, WJ; Calls, J; Bonmatin, JM; Bengsch, E; Peters, D  (2007)

Detection and localisation of picorna-like virus particles in tissues of Varroa destructor, an ectoparasite of the honey bee, Apis mellifera

Journal of Invertebrate Pathology (2007) 96 97-105
Virus-like particles, 27 nm in diameter, were observed in extracts of individual Varroa destructor mites and in sections of mite tissue. Application of a purification procedure resulted in virus preparations that were used to prepare an antiserum to detect the virus in individual mites. Immunohistology studies showed that the gastric caecae were heavily infected, whereas no immunostaining could be detected in other mite tissues or organs, like the salivary glands, brain, rectum or reproductive organs. By electron microscopy large aggregates of virus-like particles in para-crystalline lattices were found in cells of the gastric caecae. The particles, reminiscent to picorna-like viruses, occurred mainly in the cytoplasm, whereas some virus particles were sparsely scattered in vacuoles. Occasionally, particles were observed in membrane-bound vesicles or in long tubular membrane structures in the cytoplasm. The accumulation of the picornalike virus particles in the cytoplasm and the presence of the virus in membrane structures give a strong indication that the virus replicates in the mite. (c) 2007 Elsevier Inc. All rights reserved.

Virus-like particles, 27 nm in diameter, were observed in extracts of individual Varroa destructor mites and in sections of mite tissue. Application of a purification procedure resulted in virus preparations that were used to prepare an antiserum to detect the virus in individual mites. Immunohistology studies showed that the gastric caecae were heavily infected, whereas no immunostaining could be detected in other mite tissues or organs, like the salivary glands, brain, rectum or reproductive organs. By electron microscopy large aggregates of virus-like particles in para-crystalline lattices were found in cells of the gastric caecae. The particles, reminiscent to picorna-like viruses, occurred mainly in the cytoplasm, whereas some virus particles were sparsely scattered in vacuoles. Occasionally, particles were observed in membrane-bound vesicles or in long tubular membrane structures in the cytoplasm. The accumulation of the picornalike virus particles in the cytoplasm and the presence of the virus in membrane structures give a strong indication that the virus replicates in the mite. (c) 2007 Elsevier Inc. All rights reserved.


2005   References found : 4

Bonmatin, JM; Marchand, PA; Charvet, R; Moineau, I; Bengsch, ER; Colin, ME  (2005)

Quantification of imidacloprid uptake in maize crops

Journal of Agricultural and Food Chemistry (2005) 53 (13) 5336-5341
The systemic imidacloprid is one of the most used insecticides in the world for field and horticultural crops. This neurotoxicant is often used as seed-dressing, especially for maize, sunflower, and rape. Using a LC/MS/MS technique (LOQ = 1 mu g/kg and LOD = 0.1 mu g/kg), the presence of imidacloprid has been measured in maize from field samples at the time of pollen shed, from less than 0.1 mu g/kg up to 33.6 mu g/kg. Numerous random samples were collected throughout France from 2000 to 2003. The average levels of imidacloprid measured are 4.1 mu g/kg in stems and leaves, 6.6 mu g/kg in male flowers (panicles), and 2.1 mu g/kg in pollen.

The systemic imidacloprid is one of the most used insecticides in the world for field and horticultural crops. This neurotoxicant is often used as seed-dressing, especially for maize, sunflower, and rape. Using a LC/MS/MS technique (LOQ = 1 mu g/kg and LOD = 0.1 mu g/kg), the presence of imidacloprid has been measured in maize from field samples at the time of pollen shed, from less than 0.1 mu g/kg up to 33.6 mu g/kg. Numerous random samples were collected throughout France from 2000 to 2003. The average levels of imidacloprid measured are 4.1 mu g/kg in stems and leaves, 6.6 mu g/kg in male flowers (panicles), and 2.1 mu g/kg in pollen.

Colin, ME; Marchand, P; Bonmatin, JM   (2005)

Valeur et limite d’une analyse toxicologique; approche simplifiée

Abeilles & Cie (2005) 105 19-21

Bonmatin, JM   (2005)

Dossier phytosanitaires/abeilles

Abeilles et Fleurs (2005) n° 664, 19

Bonmatin, JM; Moineau, I; Charvet, R; Colin, ME; Fleche, C; Bengsch, ER  (2005)

Behaviour of imidacloprid in fields. Toxicity for honey bees

In "Environmental Chemistry: Green Chemistry and Pollutants in Ecosystems" (2005) Lichtfouse, E.; Schwarzbauer, J.; Robert, D. (Eds), 483-494
Environmental chemistry is a new, fast developing science aimed at deciphering fundamental mechanisms ruling the behaviour of pollutants in ecosystems. Applying this knowledge to current environmental issues leads to the remediation of environmental media, and to new, low energy, low emission, sustainable processes. This book describes the state-of-the-art advances regarding the pollution of water, soils, atmosphere, food and living organisms by toxic metals, fossil fuels, pesticides and other organic pollutants. Furthermore, the eco-toxicology section presents novel bio-assays to assess the toxicity of various pollutants such as dioxins and endocrine disrupters within complex media. The green chemistry section highlights novel chemical reactions based upon environmentally friendly conditions. The analytical chemistry section describes very sensitive methods which trace the fate of pollutants in complex ecosystems.

Environmental chemistry is a new, fast developing science aimed at deciphering fundamental mechanisms ruling the behaviour of pollutants in ecosystems. Applying this knowledge to current environmental issues leads to the remediation of environmental media, and to new, low energy, low emission, sustainable processes. This book describes the state-of-the-art advances regarding the pollution of water, soils, atmosphere, food and living organisms by toxic metals, fossil fuels, pesticides and other organic pollutants. Furthermore, the eco-toxicology section presents novel bio-assays to assess the toxicity of various pollutants such as dioxins and endocrine disrupters within complex media. The green chemistry section highlights novel chemical reactions based upon environmentally friendly conditions. The analytical chemistry section describes very sensitive methods which trace the fate of pollutants in complex ecosystems.


2004   References found : 5

Bonmatin, JM; Marchand, PA; Charvet, R; Colin, ME  (2004)

Biodisponibilité des insecticides systémiques en plein champs (imidaclopride et fipronil) et risques pour les pollinisateurs

Abeille de France et L’apiculteur, n° 908, 490

Bonmatin, JM; Marchand, PA; Charvet, R; Colin, ME  (2004)

Fate of systemic insecticides in fields (imidacloprid and fipronil) and risks for pollinators

First European Conference On Apidology (2004) Udine, Italy, p. 118

Charvet, R; Katouzian-Safadi, M; Colin, ME; Marchand, PA; Bonmatin, JM   (2004)

Systemic insecticides: new risks for pollinator insects

Annales Pharmaceutiques Francaises 62 (1) 29-35
Imidacloprid, a new systemic insecticide used as seed-dressing, has been widely used in France since 1994. Its application mode and its efficiency allow a significant reduction in comparison with the usual quantity of chemicals used during pulverising treatment. But the insecticide imidacloprid is suspected to have harmful effects on the pollinators as many bees have died since its introduction. Recent studies have shown that imidacloprid has chronic and sub-lethal toxicities at levels of micro g/kg or less. It was therefore necessary to detect imidacloprid at these levels in soils, plants, flowers, and pollens. With this aim, we characterised the bio-availability of imidacloprid in the environment using a new quantitative analytical method, as a basis for the evaluation of the risk for bees.

Imidacloprid, a new systemic insecticide used as seed-dressing, has been widely used in France since 1994. Its application mode and its efficiency allow a significant reduction in comparison with the usual quantity of chemicals used during pulverising treatment. But the insecticide imidacloprid is suspected to have harmful effects on the pollinators as many bees have died since its introduction. Recent studies have shown that imidacloprid has chronic and sub-lethal toxicities at levels of micro g/kg or less. It was therefore necessary to detect imidacloprid at these levels in soils, plants, flowers, and pollens. With this aim, we characterised the bio-availability of imidacloprid in the environment using a new quantitative analytical method, as a basis for the evaluation of the risk for bees.

Ongus, JR; Peters, D; Bonmatin, JM; Bengsch, E; Vlak, JM; van Oers, MM  (2004)

Complete sequence of a picorna-like virus of the genus Iflavirus replicating in the mite Varroa destructor

Journal of General Virology 85 3747-3755 Part 12
Aggregations of 27 nm virus-like particles were observed in electron microscopy images of sectioned Varroa destructor mite tissue. The scattered occurrence of individual particles and accumulation of the virions in lattices in the cytoplasm gave an apparent indication that the virus replicates in the mite. Sequence analysis of the RNA of the purified virus revealed a genome organization with high similarity to that of members of the genus Iflavirus. Phylogenetic analysis of the polymerase showed that the virus was related most closely to Deformed wing virus (DWV) and Kakugo virus (KV) of bees.

Aggregations of 27 nm virus-like particles were observed in electron microscopy images of sectioned Varroa destructor mite tissue. The scattered occurrence of individual particles and accumulation of the virions in lattices in the cytoplasm gave an apparent indication that the virus replicates in the mite. Sequence analysis of the RNA of the purified virus revealed a genome organization with high similarity to that of members of the genus Iflavirus. Phylogenetic analysis of the polymerase showed that the virus was related most closely to Deformed wing virus (DWV) and Kakugo virus (KV) of bees.

Colin, ME; Bonmatin, JM; Moineau, I; Gaimon, C; Brun, S; Vermandere, JP  (2004)

A method to quantify and analyze the foraging activity of honey bees: Relevance to the sublethal effects induced by systemic insecticides

Archives of Environmental Contamination and Toxicology 47 (3) 387-395
The assessment of agrophannaceuticals' side effects requires more realistic simulations of field conditions than those deduced from the dose-lethality relation obtained under laboratory conditions. Because the presence of sublethal doses or concentrations may also alter the behavior of foraging insects, we attempted to devise a quantifiable and accurate protocol for evidencing various alterations in free-flying bees. Such a protocol was illustrated by testing new classes of systemic insecticides. The protocol focused on video recording to quantify the foraging activity of small colonies of honey bees confined in insect-proof tunnels. The basis of the protocol was not the colony itself but the change in each colony on a specific day and between days.

The assessment of agrophannaceuticals’ side effects requires more realistic simulations of field conditions than those deduced from the dose-lethality relation obtained under laboratory conditions. Because the presence of sublethal doses or concentrations may also alter the behavior of foraging insects, we attempted to devise a quantifiable and accurate protocol for evidencing various alterations in free-flying bees. Such a protocol was illustrated by testing new classes of systemic insecticides. The protocol focused on video recording to quantify the foraging activity of small colonies of honey bees confined in insect-proof tunnels. The basis of the protocol was not the colony itself but the change in each colony on a specific day and between days.


2003   References found : 4

Katouzian-Safadi,M; Bonmatin, JM  (2003)

The use of honey in the simple and composed drugs at Rhazes

Revue D’histoire de la Pharmacie (Paris) 51 (337) 29-36
Razi or Rhazes for Latin people is one of the great scientists of ninth century. He left major works in medicine, pharmacy and in alchemy. We examine here, the use of honey by this scientist as a simple drug and as one of the essential substances included in composed medicines. That leads us to examine the notion of simple and of composed in this physician and alchemist.

Razi or Rhazes for Latin people is one of the great scientists of ninth century. He left major works in medicine, pharmacy and in alchemy. We examine here, the use of honey by this scientist as a simple drug and as one of the essential substances included in composed medicines. That leads us to examine the notion of simple and of composed in this physician and alchemist.

Ricordel, J; Bonmatin, JM  (2003)

Honey’s virtues in theriacs

Revue D’ Histoire de la Pharmacie (Paris) 51 (337) 21-28
Electuaries and theriacs include an important proportion of honey in their ingredients This one has a double purpose. It is an exicipient and a curative agent. On the other hand it is used as preservative, blinder and sweetener and on the other hand it is recommended because of its numerous healing virtues. Physicians take care of the selection and preparation's conditions to have an optimal quality of the honey and they consider its real nature got during its elaboration. Honey will be a perfect food and drug if it was not subjected to the digestion's action after its absorption.

Electuaries and theriacs include an important proportion of honey in their ingredients This one has a double purpose. It is an exicipient and a curative agent. On the other hand it is used as preservative, blinder and sweetener and on the other hand it is recommended because of its numerous healing virtues. Physicians take care of the selection and preparation’s conditions to have an optimal quality of the honey and they consider its real nature got during its elaboration. Honey will be a perfect food and drug if it was not subjected to the digestion’s action after its absorption.

Bonmatin, JM; Laprevote, O; Peypoux, F  (2003)

Diversity among microbial cyclic lipopeptides: iturins and surfactins. Activity-structure relationships to design new bioactive agents

Combinatorial Chemistry & High Throughput Screening 6 (6) 541-556
A prominent group of bioactive lipopeptides produced by Bacillus species is constituted by iturins, surfactins and lichenysins. Interest in such substances results in their exceptional surfactant power, and their valuable antifungal, antibacterial, antitumoral and anti-Mycoplasma properties. As is typical for peptidic secondary-metabolites synthesized by the polyenzymic pathway, they are produced as mixtures of components varying in the peptidic and / or in the lipidic structure. In the context of structure-activity relationships, it is possible to take advantage of the adaptability of the biosynthesis system by systematically adding selected amino acids in the culture medium of the producing bacterium. When an amino acid is used as the sole nitrogen source, it is inserted direcly into selected positions of the peptide sequence, thus amplifying the original structural microheterogeneity via a production of variants. This method revealed very efficient for increasing the amounts of preexisting variants and for building new variants of surfactins and lichenysins but totally inefficient with iturins. In this group, the peptidic diversity strictly depends on the selected strain. So far the screening remained the only method to discover new iturins. Another interesting peculiarity is the common occurrence in a single strain of two lipopeptides with different core structures such as surfactins and iturins. Taken together, these features led to an extensive metabolite pattern. Besides, engineered variants and chemical derivatives enlarged the array of available molecules. Despite the high degree of chemical similarity, the separation of variants and / or homologues was successfully achieved by reversed-phase HPLC leading to well-separated compounds ideally suited to investigation of structure-activity relationships. Improved physical techniques such as 2D-NMR and mass spectrometry allowed to describe efficiently and rapidly the composition of cyclic lipopeptides even in mixtures containing several variants. From NMR, the 3D structure and dynamics gave crucial data for fine structure-activity relationships as well as for understanding of the properties at the membrane and / or at the air / water interface. Here the role of residues was identified in the context of hydrophobic and electrostatic interactions that play a leader role. Such a comprehensive approach, based on both structural and biosynthesis knowledge, opened the way to rational design for enhanced properties and its validity was confirmed with 10 fold higher surfactant efficacy.

A prominent group of bioactive lipopeptides produced by Bacillus species is constituted by iturins, surfactins and lichenysins. Interest in such substances results in their exceptional surfactant power, and their valuable antifungal, antibacterial, antitumoral and anti-Mycoplasma properties. As is typical for peptidic secondary-metabolites synthesized by the polyenzymic pathway, they are produced as mixtures of components varying in the peptidic and / or in the lipidic structure. In the context of structure-activity relationships, it is possible to take advantage of the adaptability of the biosynthesis system by systematically adding selected amino acids in the culture medium of the producing bacterium. When an amino acid is used as the sole nitrogen source, it is inserted direcly into selected positions of the peptide sequence, thus amplifying the original structural microheterogeneity via a production of variants. This method revealed very efficient for increasing the amounts of preexisting variants and for building new variants of surfactins and lichenysins but totally inefficient with iturins. In this group, the peptidic diversity strictly depends on the selected strain. So far the screening remained the only method to discover new iturins. Another interesting peculiarity is the common occurrence in a single strain of two lipopeptides with different core structures such as surfactins and iturins. Taken together, these features led to an extensive metabolite pattern. Besides, engineered variants and chemical derivatives enlarged the array of available molecules. Despite the high degree of chemical similarity, the separation of variants and / or homologues was successfully achieved by reversed-phase HPLC leading to well-separated compounds ideally suited to investigation of structure-activity relationships. Improved physical techniques such as 2D-NMR and mass spectrometry allowed to describe efficiently and rapidly the composition of cyclic lipopeptides even in mixtures containing several variants. From NMR, the 3D structure and dynamics gave crucial data for fine structure-activity relationships as well as for understanding of the properties at the membrane and / or at the air / water interface. Here the role of residues was identified in the context of hydrophobic and electrostatic interactions that play a leader role. Such a comprehensive approach, based on both structural and biosynthesis knowledge, opened the way to rational design for enhanced properties and its validity was confirmed with 10 fold higher surfactant efficacy.

Bonmatin, JM; Moineau, I; Charvet, R; Fleche, C; Colin, ME; Bengsch, ER  (2003)

A LC/APCI-MS/MS method for analysis of imidacloprid in soils, in plants, and in pollens

Analytical Chemistry 75 (9) 2027-2033
Imidacloprid, the most used systemic insecticide, is suspected of having harmful effects on honeybees at nanogram per bee or at microgram per kilogram levels. However, there is a lack of methodology to detect imidacloprid and its metabolites at such low levels. We developed a method for the determination of low amounts of imidacloprid in soils, plants (leaves and flowers), and pollens by using HPLC coupled to tandem mass spectrometry (APCI-MS/MS). Extraction, separation, and detection were performed according to quality assurance criteria, to Good laboratory Practice, and to criteria from the directive 96/23/EC, which is designed for banned substances. The linear range of application is 0.5-20 mug/kg imidacloprid in soils, in plants, and in pollens, with a relative standard deviation of 2.9% at 1 mug/kg. The limits of detection and of quantification are LOD = 0.1 mug/kg and LOQ = 1 mug/kg, respectively. For the first time, this study permitted us to follow the fate of imidacloprid in the environment. When treated, flowers of sunflower and maize contain average values of similar to10 mug/kg imidacloprid. Ibis explains that pollens from these crops are contaminated at levels of a few micrograms per kilogram, suggesting probable deleterious effects on honeybees.

Imidacloprid, the most used systemic insecticide, is suspected of having harmful effects on honeybees at nanogram per bee or at microgram per kilogram levels. However, there is a lack of methodology to detect imidacloprid and its metabolites at such low levels. We developed a method for the determination of low amounts of imidacloprid in soils, plants (leaves and flowers), and pollens by using HPLC coupled to tandem mass spectrometry (APCI-MS/MS). Extraction, separation, and detection were performed according to quality assurance criteria, to Good laboratory Practice, and to criteria from the directive 96/23/EC, which is designed for banned substances. The linear range of application is 0.5-20 mug/kg imidacloprid in soils, in plants, and in pollens, with a relative standard deviation of 2.9% at 1 mug/kg. The limits of detection and of quantification are LOD = 0.1 mug/kg and LOQ = 1 mug/kg, respectively. For the first time, this study permitted us to follow the fate of imidacloprid in the environment. When treated, flowers of sunflower and maize contain average values of similar to10 mug/kg imidacloprid. Ibis explains that pollens from these crops are contaminated at levels of a few micrograms per kilogram, suggesting probable deleterious effects on honeybees.


2002   References found : 2

Bonmatin J.-M.  (2002)

Abeilles et insecticides: après le tournesol, le maïs

Abeille de France (2002) n° 886, 504-505

Bonmatin J.-M.  (2002)

Insecticide et pollinisateurs: une dérive de la chimie?

Sciences (2002) n° 2, 42-46


2001   References found : 4

Lecoublet, S; Bonmatin, JM; Peters, D; Bengsch, ER  (2001)

Verso la messa a punto del controllo biologico virale contro la varroasi

European Documentation, in Apiculture For Press and Information, Lapis Anno Ix 7 4-7

Lecoublet, S; Bonmatin, JM; Peters, D; Bengsch, ER  (2001)

Vers la mise au point du contrôle biologique viral contre la varroase.

Revue Française D’apiculture 618 265-7

Colin, M; Tchamitchian, M; Bonmatin, JM; Di Pasquale, S  (2001)

Presence of chitinase in adult Varroa destructor, an ectoparasitic mite of Apis mellifera

Experimental and Applied Acarology (2001) 25 (12) 947-955
The enzyme spectrum of an ectoparasitic mite of the honeybee, Varroa destructor (Anderson and Trueman) was studied using a semi-quantitative method, especially designed for complex samples which have not been purified. Exopeptidases and phosphatases are shown present. A chitinase and enzymes able to transform beta carbohydrates are also present with a large range in the intensity of the reaction. The role of the chitinase can be related to the supply of nutritional needs or/and the piercing and sucking behaviour of the adult parasite. Chitinase activity could be one factor influencing the balance between the parasite and its host.

The enzyme spectrum of an ectoparasitic mite of the honeybee, Varroa destructor (Anderson and Trueman) was studied using a semi-quantitative method, especially designed for complex samples which have not been purified. Exopeptidases and phosphatases are shown present. A chitinase and enzymes able to transform beta carbohydrates are also present with a large range in the intensity of the reaction. The role of the chitinase can be related to the supply of nutritional needs or/and the piercing and sucking behaviour of the adult parasite. Chitinase activity could be one factor influencing the balance between the parasite and its host.

Bonmatin, JM; Moineau, I; Lecoublet, S; Colin, ME; Fléché, C; Bengsch, ER  (2001)

Neurotoxiques systémiques : biodisponibilité, toxicité et risque pour les insectes pollinisateurs - le cas de l’imidaclopride -

Produits Phytosanitaires (2001) 175-181 - Editons et Presses Univiversitaires de Reims, France


2000   References found : 2

Bonmatin, JM; Moineau, I; Colin, ME; Fléché, C; Bengsch, ER  (2000)

L’insecticide imidaclopride: Biodisponibilité dans les sols et les plantes, toxicité et risque pour les abeilles.

Revue Française D’apiculture 609 360-361

Grangemard, I; Peypoux, F; Bonmatin, JM  (2000)

Rational design of new bioactive lipopeptides: Structure-activity relationships, biosynthesis and applications

Peptides 641-642 - Editor(s): EDK, Paris, France


1999   References found : 3

Peypoux, F; Bonmatin, JM; Wallach, J  (1999)

Recent trends in the biochemistry of surfactin

Applied Microbiology and Biotechnology 51 (5) 553-563
The name surfactin refers to a bacterial cyclic lipopeptide, primarily renowned for its exceptional surfactant power since it lowers the surface tension of water from 72 mN m(-1) to 27 mN m(-1) at a concentration as low as 20 mu M. Although surfactin was discovered about 30 years ago, there has been a revival of interest in this compound over the past decade, triggered by an increasing demand for effective biosurfactants for difficult contemporary ecological problems. This simple molecule also looks very promising as an antitumoral, antiviral and anti-Mycoplasma agent.

The name surfactin refers to a bacterial cyclic lipopeptide, primarily renowned for its exceptional surfactant power since it lowers the surface tension of water from 72 mN m(-1) to 27 mN m(-1) at a concentration as low as 20 mu M. Although surfactin was discovered about 30 years ago, there has been a revival of interest in this compound over the past decade, triggered by an increasing demand for effective biosurfactants for difficult contemporary ecological problems. This simple molecule also looks very promising as an antitumoral, antiviral and anti-Mycoplasma agent.

Grangemard, I; Bonmatin, JM; Bernillon, J; Das, BC; Peypoux, F  (1999)

Lichenysins G, a novel family of lipopeptide biosurfactants from Bacillus licheniformis IM 1307: Production, isolation and structural evaluation by NMR and mass spectrometry

Journal of Antibiotics 52 (4) 363-373
A series of 9 lactonic lipopeptide biosurfactants was isolated from Bacillus licheniformis IM 1307 as representatives of the lichenysin group and we propose to name them lichenysins G. They were recovered from the culture medium as complex mixtures of molecules having different peptide sequences and different structures of P-hydroxy fatty acids. Their separation was achieved by a reversed-phase HPLC method leading to eight well-separated compounds. The complete structure of individual isoforms was proposed following the results of amino acid and fatty acid analysis, LSI-MS and 2D NMR spectroscopies. Compared to surfactin, lichenysins G are at least 10 fold more efficient biosurfactants.

A series of 9 lactonic lipopeptide biosurfactants was isolated from Bacillus licheniformis IM 1307 as representatives of the lichenysin group and we propose to name them lichenysins G. They were recovered from the culture medium as complex mixtures of molecules having different peptide sequences and different structures of P-hydroxy fatty acids. Their separation was achieved by a reversed-phase HPLC method leading to eight well-separated compounds. The complete structure of individual isoforms was proposed following the results of amino acid and fatty acid analysis, LSI-MS and 2D NMR spectroscopies. Compared to surfactin, lichenysins G are at least 10 fold more efficient biosurfactants.

Mandard, N; Sy, D; Maufrais, C; Bonmatin, JM; Bulet, P; Hetru, C; Vovelle, F  (1999)

Androctonin, a novel antimicrobial peptide from scorpion Androctonus australis: Solution structure and molecular dynamics simulations in the presence of a lipid monolayer

Journal of Biomolecular Structure & Dynamics 17 (2) 367-+
Androctonin is a highly cationic antimicrobial peptide from scorpion exhibiting a broad spectrum of activities against bacteria and fungi. It contains 25 amino acids including four cysteine residues forming two disulfide bridges. We report here on the determination of its solution structure by conventional two-dimensional (2D) H-1-NMR spectroscopy and molecular modelling using distance geometry and molecular dynamics methods. The structure of androctonin involves a well-defined highly twisted anti-parallel beta-sheet with strands connected by a more variable positively charged turn. A comparison with the structure of tachyplesin I (horseshoe crab) reveals that the amphiphilic character of the protein surface of this homologous peptide is not observed in androctonin. We have undertaken a 200-ps molecular dynamics simulation study on a system including one androctonin molecule and a monolayer of DMPG (1,2-dimyristoylphosphatidylglycerol) lipids. On the basis of this simulation, the first steps of the membrane permeabilization process are discussed.

Androctonin is a highly cationic antimicrobial peptide from scorpion exhibiting a broad spectrum of activities against bacteria and fungi. It contains 25 amino acids including four cysteine residues forming two disulfide bridges. We report here on the determination of its solution structure by conventional two-dimensional (2D) H-1-NMR spectroscopy and molecular modelling using distance geometry and molecular dynamics methods. The structure of androctonin involves a well-defined highly twisted anti-parallel beta-sheet with strands connected by a more variable positively charged turn. A comparison with the structure of tachyplesin I (horseshoe crab) reveals that the amphiphilic character of the protein surface of this homologous peptide is not observed in androctonin. We have undertaken a 200-ps molecular dynamics simulation study on a system including one androctonin molecule and a monolayer of DMPG (1,2-dimyristoylphosphatidylglycerol) lipids. On the basis of this simulation, the first steps of the membrane permeabilization process are discussed.


1998   References found : 1

Mandard, N; Sodano, P; Labbe, H; Bonmatin, JM; Bulet, P; Hetru, C; Ptak, M; Vovelle, F  (1998)

Solution structure of thanatin, a potent bactericidal and fungicidal insect peptide, determined from proton two-dimensional nuclear magnetic resonance data

European Journal of Biochemistry 256 (2) 404-410
Thanatin is the first inducible insect peptide that has been found to have, at physiological concentrations, a broad ranee of activity against bacteria and fungi. Thanatin contains 21 amino acids including two cysteine residues that form a disulfide bridge. Two-dimensional (2D) H-1-NMR spectroscopy and molecular modelling have been used to determine its three-dimensional (3D) structure in water. Thanatin adopts a well-defined anti-parallel beta-sheet structure from residue 8 to the C-terminus, including the disulfide bridge. In spire of the presence of two proline residues, there is a large degree of structural variability in the N-terminal segment. The structure of thanatin is quite different from the known structures of other insect defence peptides, such as antibactarial defensin and antifungal drosomycin. It has more similarities with the structures of various peptides from different origins, such as brevinins, protegrins and tachyplesins. which have a two-stranded beta-sheet stabilized by one or two disulfide bridges. Combined with activity test experiments on several truncated isoforms of thanatin, carried out by Fehlbaum et al. [Fehlbaum, P., Bulet, P., Chernysh, S., Briand, J. P., Roussel, J. P., Letellier. L., Hetru, C. & Hoffmann. J. (1996) Pmc. Natl Acad Sci. USA 93, 1221-1225], our structural study evidences the importance of the P-sheet structure and also sn nests hat anti-Gram-negative activity involves a site formed by the Arg20 side-chain embedded in a hydrophobic cluster.

Thanatin is the first inducible insect peptide that has been found to have, at physiological concentrations, a broad ranee of activity against bacteria and fungi. Thanatin contains 21 amino acids including two cysteine residues that form a disulfide bridge. Two-dimensional (2D) H-1-NMR spectroscopy and molecular modelling have been used to determine its three-dimensional (3D) structure in water. Thanatin adopts a well-defined anti-parallel beta-sheet structure from residue 8 to the C-terminus, including the disulfide bridge. In spire of the presence of two proline residues, there is a large degree of structural variability in the N-terminal segment. The structure of thanatin is quite different from the known structures of other insect defence peptides, such as antibactarial defensin and antifungal drosomycin. It has more similarities with the structures of various peptides from different origins, such as brevinins, protegrins and tachyplesins. which have a two-stranded beta-sheet stabilized by one or two disulfide bridges. Combined with activity test experiments on several truncated isoforms of thanatin, carried out by Fehlbaum et al. [Fehlbaum, P., Bulet, P., Chernysh, S., Briand, J. P., Roussel, J. P., Letellier. L., Hetru, C. & Hoffmann. J. (1996) Pmc. Natl Acad Sci. USA 93, 1221-1225], our structural study evidences the importance of the P-sheet structure and also sn nests hat anti-Gram-negative activity involves a site formed by the Arg20 side-chain embedded in a hydrophobic cluster.


1997   References found : 3

Landon, C; Sodano, P; Cornet, B; Bonmatin, JM; Kopeyan, C; Rochat, H; Vovelle, F; Ptak, M  (1997)

Refined solution structure of the anti-mammal and anti-insect LqqIII scorpion toxin: Comparison with other scorpion toxins

Proteins-Structure Function and Genetics 28 (3) 360-374
The solution structure of the anti-mammal and anti-insect LqqIII toxin from the scorpion Leiurus quinquestriatus quinquestriatus was refined and compared with other long-chain scorpion toxins, This structure, determined by H-1-NMR and molecular modeling, involves an a-helix (18-29) linked to a three-stranded ß-sheet (2-6, 33-39, and 43-51) by two disulfide bridges, The average RMSD between the 15 best structures and the mean structure is 0.71 Angstrom for C a atoms, Comparison between LqqIII, the potent anti-mammal AaHII, and the weakly active variant-3 toxins revealed that the LqqIII three-dimensional structure is closer to that of AaHII than to the variant-3 structure, Moreover, striking analogies were observed between the electrostatic and hydrophobic potentials of LqqIII and AaHII.

The solution structure of the anti-mammal and anti-insect LqqIII toxin from the scorpion Leiurus quinquestriatus quinquestriatus was refined and compared with other long-chain scorpion toxins, This structure, determined by H-1-NMR and molecular modeling, involves an a-helix (18-29) linked to a three-stranded ß-sheet (2-6, 33-39, and 43-51) by two disulfide bridges, The average RMSD between the 15 best structures and the mean structure is 0.71 Angstrom for C a atoms, Comparison between LqqIII, the potent anti-mammal AaHII, and the weakly active variant-3 toxins revealed that the LqqIII three-dimensional structure is closer to that of AaHII than to the variant-3 structure, Moreover, striking analogies were observed between the electrostatic and hydrophobic potentials of LqqIII and AaHII.

Grangemard, I; Peypoux, F; Wallach, J; Das, BC; Labbe, H; Caille, A; Genest, M; Maget-Dana, R; Ptak, M; Bonmatin, JM  (1997)

Lipopeptides with improved properties: Structure by NMR, purification by HPLC and structure-activity relationships of new isoleucyl-rich surfactins

Journal of Peptide Science 3 (2) 145-154
The biosynthesis of bacterial isoleucyl-rich surfactins was controlled by supplementation of L-isoleucine to the culture medium. Two new variants, the [Ile4,7]- and [Ile2,4,7]surfactins, were thus produced by Bacillus subtilis and their separation was achieved by reverse-phase HPLC. Amino acids of the heptapeptide moiety were analysed by chemical methods, and the lipid moiety was identified to B-hydroxy anteiso pentadecanoic acid by combined GC/MS. Sequences were established on the basis of two-dimensional NMR data. Because conformational parameters issuing from NMR spectra suggested that the cyclic backbone fold was globally conserved in the new variants, structure-activity relationships were discussed in details on the basis of the three-dimensional model of surfactin in solution.

The biosynthesis of bacterial isoleucyl-rich surfactins was controlled by supplementation of L-isoleucine to the culture medium. Two new variants, the [Ile4,7]- and [Ile2,4,7]surfactins, were thus produced by Bacillus subtilis and their separation was achieved by reverse-phase HPLC. Amino acids of the heptapeptide moiety were analysed by chemical methods, and the lipid moiety was identified to B-hydroxy anteiso pentadecanoic acid by combined GC/MS. Sequences were established on the basis of two-dimensional NMR data. Because conformational parameters issuing from NMR spectra suggested that the cyclic backbone fold was globally conserved in the new variants, structure-activity relationships were discussed in details on the basis of the three-dimensional model of surfactin in solution.

Mandard, N; Sodano, P; Labbé, H; Bonmatin, JM; Ptak, M; Vovelle, F  (1997)

Solution structure of thanatin, an insect defense peptide with antimicrobial properties

European Biophysical Journal 26 (1) 137


1996   References found : 1

Landon, C; Cornet, B; Bonmatin, JM; Kopeyan, C; Rochat, H; Vovelle, F; Ptak, M  (1996)

H-1-NMR-derived secondary structure and the overall fold of the potent anti-mammal and anti-insect toxin III from the scorpion Leiurus quinquestriatus quinquestriatus

European Journal of Biochemistry 236 (2) 395-404
We describe the secondary structure and the overall fold of toxin III from the venom of the scorpion Leiurus quinquestriatus quinquestriatus determined using two-dimensional-1H-NMR spectroscopy. This protein, which contains 64 amino acids and 4 disulfide bridges, belongs to the long-chain toxin category and is highly toxic to both mammals and insects. The overall fold was determined on the basis of 1208 inter-proton-distance restraints derived from NOE measurements and 90 Ψ, Φ dihedral-angle restraints derived from NOE connectivities and 3JNH-αH coupling constants using the HABAS program. This fold, which mainly consists of an α-helix packed against a small antiparallel three-stranded β-sheet, and of several turns and loops, is similar to that of other long-chain scorpion toxins. Aromatic and non-polar residues form several patches on the surface of the protein which alternate with patches of charged and polar residues. Such a topology should be important in the interactions of toxin III with sodium channels in membranes. Two weakly constrained loops introduce some flexibility to the structure which could be related to the activity of this toxin. The central core of toxin III is compared with the cysteine-stabilized αβ motif (an α-helix connected to a β-sheet through two disulfide bridges) found in insect defensins and plant thionins. Defensins and thionins are small proteins (≈40–50 amino acid residues) containing three or four disulfide bridges, respectively. This comparison confirms that the cysteine-stabilized αβ motif is a common core to a number of small proteins from different origins and having different activities.

We describe the secondary structure and the overall fold of toxin III from the venom of the scorpion Leiurus quinquestriatus quinquestriatus determined using two-dimensional-1H-NMR spectroscopy. This protein, which contains 64 amino acids and 4 disulfide bridges, belongs to the long-chain toxin category and is highly toxic to both mammals and insects. The overall fold was determined on the basis of 1208 inter-proton-distance restraints derived from NOE measurements and 90 Ψ, Φ dihedral-angle restraints derived from NOE connectivities and 3JNH-αH coupling constants using the HABAS program. This fold, which mainly consists of an α-helix packed against a small antiparallel three-stranded β-sheet, and of several turns and loops, is similar to that of other long-chain scorpion toxins. Aromatic and non-polar residues form several patches on the surface of the protein which alternate with patches of charged and polar residues. Such a topology should be important in the interactions of toxin III with sodium channels in membranes. Two weakly constrained loops introduce some flexibility to the structure which could be related to the activity of this toxin. The central core of toxin III is compared with the cysteine-stabilized αβ motif (an α-helix connected to a β-sheet through two disulfide bridges) found in insect defensins and plant thionins. Defensins and thionins are small proteins (≈40–50 amino acid residues) containing three or four disulfide bridges, respectively. This comparison confirms that the cysteine-stabilized αβ motif is a common core to a number of small proteins from different origins and having different activities.


1995   References found : 5

Magetdana, R; Bonmatin, JM; Hetru, C; Ptak, M; Maurizot, JC  (1995)

The secondary structure of the insect defensin-A depends on its environment - a circular-dichroism study

Biochimie 77 (4) 240-244
Defensin A is an inducible antibacterial protein isolated from the larvae of Phormia terranovae. The conformation of defensin A has been previously determined by two-dimensional(1)H-NMR for concentrations in the range of 4-8 mM in water (Bonmatin JM et al (1992)J Biomol NMR 2, 235-256). CD spectroscopic data of defensin A at lower concentrations (10(-5) to 10(-3) M) are reported herein. The ellipticity in the 200-240 nm wavelength range for various solvents varies as follows: acetonitrile

Defensin A is an inducible antibacterial protein isolated from the larvae of Phormia terranovae. The conformation of defensin A has been previously determined by two-dimensional(1)H-NMR for concentrations in the range of 4-8 mM in water (Bonmatin JM et al (1992)J Biomol NMR 2, 235-256). CD spectroscopic data of defensin A at lower concentrations (10(-5) to 10(-3) M) are reported herein. The ellipticity in the 200-240 nm wavelength range for various solvents varies as follows: acetonitrile

Cornet, B; Bonmatin, JM; Ptak, M; Vovelle, F  (1995)

Refined 3-dimensional structure of insect defensin-a in water from NMR data

Journal of Trace and Microprobe Techniques 13 (3) 335-336
Background: Insect defensin A is a basic 4 kDa protein secreted by Phormia terranovae larvae in response to bacterial challenges or injuries. Previous biological tests suggest that the bacterial cytoplasmic membrane is the target of defensin A. The structural study of this protein is the first step towards establishing a structure–activity relationship and forms the basis for understanding its antibiotic activity at the molecular level. 

Results We describe a refined model of the three-dimensional structure of defensin A derived from an extensive analysis of 786 inter-proton nuclear Overhauser effects. The backbone fold involves an N-terminal loop and an α-helical fragment followed by an antiparallel β-structure. The helix and the β-structure are connected by two of the three disulphide bridges present in defensin A, forming a so-called ‘cysteine-stabilized α β' (CS α β) motif. The N-terminal loop, which is locally well defined, can occupy different positions with respect to the other moieties of the molecule. 

Conclusion The CSα β motif, which forms the core of the defensin A structure, appears to be a common organization for several families of small proteins with toxic properties. The distribution of amino acid side chains in the protein structure creates several hydrophobic or hydrophilic patches. This leads us to propose that the initial step in the action of positively charged defensin A molecules with cytoplasmic membranes may involve interactions with acidic phospholipids.

Background: Insect defensin A is a basic 4 kDa protein secreted by Phormia terranovae larvae in response to bacterial challenges or injuries. Previous biological tests suggest that the bacterial cytoplasmic membrane is the target of defensin A. The structural study of this protein is the first step towards establishing a structure–activity relationship and forms the basis for understanding its antibiotic activity at the molecular level.

Results We describe a refined model of the three-dimensional structure of defensin A derived from an extensive analysis of 786 inter-proton nuclear Overhauser effects. The backbone fold involves an N-terminal loop and an α-helical fragment followed by an antiparallel β-structure. The helix and the β-structure are connected by two of the three disulphide bridges present in defensin A, forming a so-called ‘cysteine-stabilized α β’ (CS α β) motif. The N-terminal loop, which is locally well defined, can occupy different positions with respect to the other moieties of the molecule.

Conclusion The CSα β motif, which forms the core of the defensin A structure, appears to be a common organization for several families of small proteins with toxic properties. The distribution of amino acid side chains in the protein structure creates several hydrophobic or hydrophilic patches. This leads us to propose that the initial step in the action of positively charged defensin A molecules with cytoplasmic membranes may involve interactions with acidic phospholipids.

Cornet, B; Bonmatin, JM; Hetru, C; Hoffmann, JA; Ptak, M; Vovelle, F  (1995)

Refined 3-dimensional solution structure of insect defensin-a

Structure 3 (5) 435-448
Background: Insect defensin A is a basic 4 kDa protein secreted by Phormia terranovae larvae in response to bacterial challenges or injuries. Previous biological tests suggest that the bacterial cytoplasmic membrane is the target of defensin A. The structural study of this protein is the first step towards establishing a structure-activity relationship and forms the basis for understanding its antibiotic activity at the molecular level. Results: We describe a refined model of the three-dimensional structure of defensin A derived from an extensive analysis of 786 inter-proton nuclear Overhauser effects. The backbone fold involves an N-terminal loop and an alpha-helical fragment followed by an antiparallel beta-structure.

Background: Insect defensin A is a basic 4 kDa protein secreted by Phormia terranovae larvae in response to bacterial challenges or injuries. Previous biological tests suggest that the bacterial cytoplasmic membrane is the target of defensin A. The structural study of this protein is the first step towards establishing a structure-activity relationship and forms the basis for understanding its antibiotic activity at the molecular level. Results: We describe a refined model of the three-dimensional structure of defensin A derived from an extensive analysis of 786 inter-proton nuclear Overhauser effects. The backbone fold involves an N-terminal loop and an alpha-helical fragment followed by an antiparallel beta-structure.

Bonmatin, JM; Labbe, H; Grangemard, I; Peypoux, F; Magetdana, R; Ptak, M; Michel, G  (1995)

Production, isolation and characterization of [leu(4)]surfactins and [ile(4)]surfactins from bacillus-subtilis

Letters in Peptide Science 2 (1) 41-47
Bacillus subtilis coproduces several surfactin variants that are powerful biosurfactants and have potential applications in biology and industry. A single amino acid substitution in the heptapeptide moiety of surfactins strongly modifies their properties. To better establish structure-activity relationships and to search new variants with enhanced properties, Bacillus subtilis was grown into two modified culture media. Two new variants were isolated by chromatographic methods and studied by NMR spectroscopy. As planned, modifications consisted in the substitution of the L-valine residue at the fourth position by a more hydrophobic residue, i.e., leucine or isoleucine. These [Leu(4)]- and [Ile(4)]surfactins have a higher affinity for hydrophobic solvents and a twice improved surfactant power. Structure-property correlations were confirmed by analysis of the hydrophobic residue distribution in the three-dimensional model of the structure of surfactin in solution.

Bacillus subtilis coproduces several surfactin variants that are powerful biosurfactants and have potential applications in biology and industry. A single amino acid substitution in the heptapeptide moiety of surfactins strongly modifies their properties. To better establish structure-activity relationships and to search new variants with enhanced properties, Bacillus subtilis was grown into two modified culture media. Two new variants were isolated by chromatographic methods and studied by NMR spectroscopy. As planned, modifications consisted in the substitution of the L-valine residue at the fourth position by a more hydrophobic residue, i.e., leucine or isoleucine. These [Leu(4)]- and [Ile(4)]surfactins have a higher affinity for hydrophobic solvents and a twice improved surfactant power. Structure-property correlations were confirmed by analysis of the hydrophobic residue distribution in the three-dimensional model of the structure of surfactin in solution.

Faucon, JF; Bonmatin, JM; Dufourcq, J; Dufourc, EJ  (1995)

Acyl-chain length dependence in the stability of melittin-phosphatidylcholine complexes - a light-scattering and p-31-NMR study

Biochimica et Biophysica Acta-Biomembranes 1234 (2) 235-243
Light scattering and P-31-NMR have been used to monitor the effect of the bee-toxin, melittin, on phosphatidylcholine (PC) bilayers of variable acyl chain length (from C-16:0 to C-20:0). Melittin interacts with all lipids provided the interaction is initiated in the lipid fluid phase. For low-to-moderate amounts of toxin (lipid-peptide molar ratios, R(i) greater than or equal to 15), the system takes the form of large spheroidal vesicles, in the fluid phase, whose radius increases from 750 Angstrom A with dipalmitoyl-PC (DPPC) to 1500 Angstrom A with diarachinoyl-PC (DAPC). These vesicles fragment into small discoids of 100-150 Angstrom A radius when the system is cooled down below T-c (the gel-to-fluid phase transition temperature).

Light scattering and P-31-NMR have been used to monitor the effect of the bee-toxin, melittin, on phosphatidylcholine (PC) bilayers of variable acyl chain length (from C-16:0 to C-20:0). Melittin interacts with all lipids provided the interaction is initiated in the lipid fluid phase. For low-to-moderate amounts of toxin (lipid-peptide molar ratios, R(i) greater than or equal to 15), the system takes the form of large spheroidal vesicles, in the fluid phase, whose radius increases from 750 Angstrom A with dipalmitoyl-PC (DPPC) to 1500 Angstrom A with diarachinoyl-PC (DAPC). These vesicles fragment into small discoids of 100-150 Angstrom A radius when the system is cooled down below T-c (the gel-to-fluid phase transition temperature).


1994   References found : 2

Bonmatin, JM; Genest, M; Labbe, H; Ptak, M  (1994)

Solution 3-dimensional structure of surfactin - a cyclic lipopeptide studied by h-1-NMR, distance geometry, and molecular-dynamics

Biopolymers 34 (7) 975-986
The solution three-dimensional structure of the protonated [Leu7]-surfactin, an heptapeptide extracted from Bacillus subtilis, has been determined from two-dimensional H-1-nmr performed in H-2(6)-dimethylsulfoxide and combined with molecular modeling. Experimental data included 9 coupling constants, 61 nuclear Overhauser effect derived distances, NH temperature coefficients, and C-13 relaxation times. Two distance geometry (DISMAN) protocols converged toward models of the structure and the best of them were refined by restrained and unrestrained molecular dynamics (GROMOS). Two structures in accord with the set of experimental constraints are presented. Both are characterized by a ''horse saddle'' topology for ring atoms on which are attached the two polar Glu and Asp side chains showing an orientation clearly opposite to that of the C-11-13 aliphatic chain. Amphipathic and surface properties of surfactin are certainly related to the existence of such minor polar and a major hydrophobic domains. The particular ''claw'' configuration of acidic residues observed in surfactin gives important clues for the understanding of its cation binding and transporting ability. (C) 1994 John Wiley and Sons, Inc.

The solution three-dimensional structure of the protonated [Leu7]-surfactin, an heptapeptide extracted from Bacillus subtilis, has been determined from two-dimensional H-1-nmr performed in H-2(6)-dimethylsulfoxide and combined with molecular modeling. Experimental data included 9 coupling constants, 61 nuclear Overhauser effect derived distances, NH temperature coefficients, and C-13 relaxation times. Two distance geometry (DISMAN) protocols converged toward models of the structure and the best of them were refined by restrained and unrestrained molecular dynamics (GROMOS). Two structures in accord with the set of experimental constraints are presented. Both are characterized by a ’’horse saddle’’ topology for ring atoms on which are attached the two polar Glu and Asp side chains showing an orientation clearly opposite to that of the C-11-13 aliphatic chain. Amphipathic and surface properties of surfactin are certainly related to the existence of such minor polar and a major hydrophobic domains. The particular ’’claw’’ configuration of acidic residues observed in surfactin gives important clues for the understanding of its cation binding and transporting ability. (C) 1994 John Wiley and Sons, Inc.

Peypoux, F; Bonmatin, JM; Labbe, H; Grangemard, I; Das, BC; Ptak, M; Wallach, J; Michel, G  (1994)

[ala4]surfactin, a novel isoform from bacillus-subtilis studied by mass and NMR spectroscopies

European Journal of Biochemistry 224 (1) 89-96
When Bacillus subtilis S 499 was grown on a culture medium containing L-alanine as nitrogen source, a mixture of surfactins was obtained. Suitable chromatographic conditions allowed the separation of isoforms. Among these compounds, a new variant of surfactin was isolated and its structure was established by chemical and spectrometric methods, especially by NMR spectrometry. It contains a peptide sequence which differs from that of standard surfactin by the replacement of the L-valine residue by L-alanine residue in position 4. The folding mode of [Ala4]surfactin as deduced from NMR results was compared with that of standard surfactin and the structure/properties relationship issuing from the study of this new isoform is discussed.

When Bacillus subtilis S 499 was grown on a culture medium containing L-alanine as nitrogen source, a mixture of surfactins was obtained. Suitable chromatographic conditions allowed the separation of isoforms. Among these compounds, a new variant of surfactin was isolated and its structure was established by chemical and spectrometric methods, especially by NMR spectrometry. It contains a peptide sequence which differs from that of standard surfactin by the replacement of the L-valine residue by L-alanine residue in position 4. The folding mode of [Ala4]surfactin as deduced from NMR results was compared with that of standard surfactin and the structure/properties relationship issuing from the study of this new isoform is discussed.


1993   References found : 1

Dufourcq, J; Dufourc, EJ; Maillet, JC; Cornut, I; Thiaudiere, E; Bonmatin, JM  (1993)

Peptide-induced changes in structure, dynamic and barrier properties of liposomes and membranes

Phosphorus Sulfur and Silicon and The Related Elements 77 (1-4) 665-668
Peptides which have the plasma membrane as a target may induce colloid osmotic lysis of cells. This is reflected by changes in phospholipid structure and dynamics as documented by spectroscopic methods and by modifications of their supramolecular properties such as phase stability, vesicularization, fusion and micellization. From similar changes induced both on model systems and on natural membranes, mechanisms are proposed for biological membrane destabilization.

Peptides which have the plasma membrane as a target may induce colloid osmotic lysis of cells. This is reflected by changes in phospholipid structure and dynamics as documented by spectroscopic methods and by modifications of their supramolecular properties such as phase stability, vesicularization, fusion and micellization. From similar changes induced both on model systems and on natural membranes, mechanisms are proposed for biological membrane destabilization.


1992   References found : 2

Bonamtin, JM; Genest, M; Petit, MC; Gincel, E; Simorre, JP; Cornet, B; Gallet, X; Caille, A; Labbe, H; Vovelle, F; Ptak, M  (1992)

Progress in multidimensional NMR investigations of peptide and protein 3-d structures in solution - from structure to functional-aspects

Biochimie 74 (9-10) 825-836
2-D and 3-D NMR techniques were used to investigate the conformations in solution of several peptides and proteins for which crystalline structures are not available yet. Insect defensin A is a small (40 aa) antibiotic protein exhibiting a characteristic 'loop-helix-beta-sheet' structure. A striking analogy was found with charybdotoxin, a scorpion toxin in which a CSH (cysteine stabilized alpha-helix) motif is also present. Wheat phospholipid transfer protein (PLTP) (90 aa) has a 3-D structure resulting from the packing of four helices and of a C-terminal less well-defined fragment. Preliminary results show that PLTP forms a complex with lyso-PC and that such an interaction results in a conformational change affecting principally the C-terminal half of the protein. A last example is given with surfactin, a lipopeptide biosurfactant from bacterial origin. Its protonated form shows a very compact structure in which the two acidic residues located on the top of a 'horse saddle' topology face each other, whereas the ionized form could adopt a more extended conformation. A common property of these compounds is their capacity to interact with lipids. The present structural data open the way for a further establishment of structure-activity relationships.

2-D and 3-D NMR techniques were used to investigate the conformations in solution of several peptides and proteins for which crystalline structures are not available yet. Insect defensin A is a small (40 aa) antibiotic protein exhibiting a characteristic ’loop-helix-beta-sheet’ structure. A striking analogy was found with charybdotoxin, a scorpion toxin in which a CSH (cysteine stabilized alpha-helix) motif is also present. Wheat phospholipid transfer protein (PLTP) (90 aa) has a 3-D structure resulting from the packing of four helices and of a C-terminal less well-defined fragment. Preliminary results show that PLTP forms a complex with lyso-PC and that such an interaction results in a conformational change affecting principally the C-terminal half of the protein. A last example is given with surfactin, a lipopeptide biosurfactant from bacterial origin. Its protonated form shows a very compact structure in which the two acidic residues located on the top of a ’horse saddle’ topology face each other, whereas the ionized form could adopt a more extended conformation. A common property of these compounds is their capacity to interact with lipids. The present structural data open the way for a further establishment of structure-activity relationships.

Bonmatin, JM; Bonnat, JL; Gallet, X; Vovelle, F; Ptak, M; Reichhart, JM; Hoffmann, JA; Keppi, E; Legrain, M; Achstetter, T  (1992)

2-dimensional h-1-NMR study of recombinant insect defensin-a in water - resonance assignments, secondary structure and global folding

Journal of Biomolecular NMR 2 (3) 235-256
A 500 MHz 2D H-1 NMR study of recombinant insect defensin A is reported. This defense protein of 40 residues contains 3 disulfide bridges, is positively charged and exhibits antibacterial properties. 2D NMR maps of recombinant defensin A were fully assigned and secondary structure elements were localized. The set of NOE connectivities, 3J(NH-alpha-H) coupling constants as well as H-1/H-2 exchange rates and DELTA-delta/DELTA-T temperature coefficients of NH protons strongly support the existence of an alpha-helix (residues 14-24) and of an antiparallel beta-sheet (residues 27-40). Models of the backbone folding were generated by using the DISMAN program and energy refined by using the AMBER program.

A 500 MHz 2D H-1 NMR study of recombinant insect defensin A is reported. This defense protein of 40 residues contains 3 disulfide bridges, is positively charged and exhibits antibacterial properties. 2D NMR maps of recombinant defensin A were fully assigned and secondary structure elements were localized. The set of NOE connectivities, 3J(NH-alpha-H) coupling constants as well as H-1/H-2 exchange rates and DELTA-delta/DELTA-T temperature coefficients of NH protons strongly support the existence of an alpha-helix (residues 14-24) and of an antiparallel beta-sheet (residues 27-40). Models of the backbone folding were generated by using the DISMAN program and energy refined by using the AMBER program.


1991   References found : 2

Malon, P; Bonmatin, JM; Brack, A  (1991)

Synthesis and characterization of cyclic-peptides with hydrolytic activity

Tetrahedron Letters 32 (39) 5337-5340
Two cyclic peptides have been prepared and characterized by MS and NMR. The linear precursors have been obtained by solid phase synthesis and the cyclization step was achieved using the BOP reagent. They increase markedly the rate of hydrolysis of oligoribonucleotides.

Two cyclic peptides have been prepared and characterized by MS and NMR. The linear precursors have been obtained by solid phase synthesis and the cyclization step was achieved using the BOP reagent. They increase markedly the rate of hydrolysis of oligoribonucleotides.

Peypoux, F; Bonmatin, JM; Labbe, H; Das, BC; Ptak, M; Michel, G  (1991)

Isolation and characterization of a new variant of surfactin, the [val7]surfactin

European Journal of Biochemistry 202 (1) 101-106
Reinvestigation of surfactin, a previously studied peptidolipid surfactant from Bacillus subtilis, by fast-atom-bombardment mass spectrometry and H-1-NMR spectroscopy, as well as by chemical methods, revealed the presence of a closely related second constituent. This new compound, [Val7]surfactin, differs from the known surfactin by the C-terminal amino acid residue which is valine instead of leucine.

Reinvestigation of surfactin, a previously studied peptidolipid surfactant from Bacillus subtilis, by fast-atom-bombardment mass spectrometry and H-1-NMR spectroscopy, as well as by chemical methods, revealed the presence of a closely related second constituent. This new compound, [Val7]surfactin, differs from the known surfactin by the C-terminal amino acid residue which is valine instead of leucine.


1990   References found : 1

Bonmatin, JM; Smith, ICP; Jarrell, HC; Siminovitch, DJ  (1990)

Use of a comprehensive approach to molecular-dynamics in ordered lipid systems - cholesterol reorientation in oriented lipid bilayers - a h-2 NMR relaxation case-study

Journal of The American Chemical Society 112 (5) 1697-1704


1989   References found : 1

Dufour,c EJ; Bonmatin, JM; Dufourcq, J  (1989)

Membrane-structure and dynamics by h-2-NMR and p-31-NMR - effects of amphipatic peptidic toxins on phospholipid and biological-membranes

Biochimie 71 (1) 117-123


1988   References found : 1

Bonmatin, JM; Smith, ICP; Jarrell, HC; Siminovitch, DJ  (1988)

Orientation dependence of h-2 NMR spin-lattice relaxation rates for cholesterol in macroscopically oriented multibilayers

Journal of The American Chemical Society 110 (26) 8693-8695