Catégorie d'actualités: significant publications

A butterfly peptide to combat resistant fungi

A promising avenue for better crop protection and perhaps even for treating certain diseases, as reported by CNRS Chimie.

Fungal infections represent a major global health problem, with increasing resistance to currently available antifungal molecules. Targeting glucosylceramides (GlcCer), which are functionally essential glycosphingolipids present in fungal membranes, represents a promising strategy for the development of new antifungal agents.

GlcCer are associated with the antifungal activity of certain antimicrobial peptides found in plants and insects, known as defensins. The ETD151 peptide, optimised from butterfly defensins, is active against a range of fungal pathogens of interest to human health and agriculture. For example, the researchers have previously shown that ETD151 induces a multifaceted mechanism of action on Botrytis cinerea, a multi-resistant phytopathogenic fungus used here as a model (Aumer et al. 2020).

This multifaceted mechanism of action makes ETD151 a promising candidate for combating fungal resistance. The researchers took up the challenge of identifying its molecular target. They showed that the ETD151 peptide binds at the molecular level to GlcCer and localises preferentially to the membrane, where it induces various toxic effects. Identifying its molecular target and understanding the mode of action of ETD151 opens up new prospects for human health and crop protection.

Reference :
O. Kharrat, Y. Yamaryo-Botté, R. Nasreddine, S. Voisin, T. Aumer, B.P.A. Cammue, J. Madinier, T. Knobloch, K. Thevissen, R. Nehmé, V. Aucagne, C. Botté, P. Bulet, & C. Landon.
The antimicrobial activity of ETD151 defensin is dictated by the presence of glycosphingolipids in the targeted organisms.
Proc. Natl. Acad. Sci. U.S.A. (2025) 122 (7) e2415524122, https://doi.org/10.1073/pnas.2415524122.

Combination of nanomedicine and biophysics methods to characterize mRNA liposomes

This new optimised version of liposomes has been reported by CNRS Chimie on its website.

The development of lipid-based mRNA delivery systems has significantly advanced mRNA-based therapies. Liposomes, in particular histidylated liposomes (LYX), have been shown to be effective in delivering nucleic acids. In this study, LYX liposomes were optimised by adding a freeze-drying and extrusion step, resulting in improved homogeneity and storage stability. LYX liposomes maintained their size (150 ± 10 nm) and polydispersity index (0.10 ± 0.02) for up to a year at 4°C, while preserving their transfection efficiency. They exhibit a high mRNA encapsulation rate (∼95%) and protect it from degradation by RNases. The lamellar organisation was confirmed by small-angle X-ray scattering and CryoTEM. These liposomes allow efficient transfection of cell lines and primary cells, albeit with lower efficiency than commercial vectors, due to slower cell internalisation and reduced endosomal escape. They have demonstrated their ability to deliver mRNA encoding the therapeutic molecules BMP2 and BMP9, leading to the production of functional proteins capable of inducing BMP signalling. In vivo studies have also confirmed their potential for mRNA delivery when incorporated into hydrogels and implanted subcutaneously in mice. These results show that LYX liposomes are a promising and versatile platform for mRNA delivery in therapeutic applications.

This work involved laboratories from two institutes: the Centre de Biophysique Moléculaire (CNRS Chimie) and the Laboratoire de Biologie, Bioingénierie et Bioimagerie Ostéo-Articulaires (CNRS Ingénierie).

Reference:
Albert Ngalle Loth, Manon Maroquenne, Ayoub Medjmedj, Franck Coste, Thomas Bizien, Chantal Pichon, Delphine Logeart-Avramoglou, Federico Perche.
Structural and functional characterization of a histidylated liposome for mRNA deliveryStructural and functional characterization of a histidylated liposome for mRNA delivery.
Journal of Controlled Release (2025) Volume 379, pages 164-176, doi: 10.1016/j.jconrel.2025.01.010.

Improved protocol for metabolite extraction and identification of respiratory quinones in extremophilic Archaea grown on mineral materials.

We investigated the metabolome of the iron- and sulfur-oxidizing, extremely thermoacidophilic archaeon Metallosphaera sedula grown on mineral pyrite (FeS2). The extraction of organic materials from these microorganisms is a major challenge because of the tight contact and interaction between cells and mineral materials. Therefore, we applied an improved protocol to break the microbial cells and separate their organic constituents from the mineral surface, to extract lipophilic compounds through liquid–liquid extraction, and performed metabolomics analyses using MALDI-TOF MS and UHPLC-UHR-Q/TOF. Using this approach, we identified several molecules involved in central carbon metabolism and in the modified Entner-Doudoroff pathway found in Archaea, sulfur metabolism-related compounds, and molecules involved in the adaptation of M. sedula to extreme environments, such as metal tolerance and acid resistance. Furthermore, we identified molecules involved in microbial interactions, i.e., cell surface interactions through biofilm formation and cell–cell interactions through quorum sensing, which relies on messenger molecules for microbial communication. Moreover, we successfully extracted and identified different saturated thiophene-bearing quinones using software for advanced compound identification (MetaboScape). These quinones are respiratory chain electron carriers in M. sedula, with biomarker potential for life detection in extreme environmental conditions.

Reference :
Gfellner SV, Colas C, Gabant G, Groninga J, Cadene M, Milojevic T. Improved protocol for metabolite extraction and identification of respiratory quinones in extremophilic Archaea grown on mineral materials. Front Microbiol. 2025 Jan 8;15:1473270. doi: 10.3389/fmicb.2024.1473270

Will it be possible to soon detect copper by non invasive imaging?

In this work, in collaboration with chemists from the Institut de Chimie de Strasbourg (CNRS/Université de Strasbourg), we have designed and studied a smart MRI probe; which is switched on in the presence of copper. The design of such probes is a real challenge as free Cu(II) in vivo is present in very low quantities, typically lower than Zn(II), another physiological cation. It is therefore of prime importance to conceive probes with a maximal turn on response in the presence of Cu(II), and an excellent selectivity towards Zn(II). The probes are typically composed of an MRI active site, a linker and a Cu(II) binding site. The use of small complexing units for Cu(II) binding makes it very difficult to obtain a good selectivity. Here, we have used a bioinspired approach where the Cu(II) binding site is based on the ATCUN motif, a small peptide that binds Cu(II) in the blood. Thanks to this design, the probe displays an unprecedented turn on response, and importantly an excellent selectivity for Cu(II) vs Zn(II). Phantom MRI images obtained closed to physiological conditions show a bright contrast, illustrating the potential of such probes.

Reference :
A Bioinspired Cu2+-Responsive Magnetic Resonance Imaging Contrast Agent with Unprecedented Turn-On Response and Selectivity
Katharina Zimmeter, Agnès Pallier, Bertrand Vileno, Martina Sanadar, Frédéric Szeremeta, Carlos Platas-Iglesias, Peter Faller, Célia S. Bonnet and Angélique Sour
Inorganic Chemistry - Vol 63 - Issue 49 - 23067−23076

Multiplex imaging in the NIR-II window with lanthanide-based molecular agents: a dream or a reality?

In this work we have created a new family of lanthanide-based molecular imaging agents that can be used for multiplex imaging in the second near-infrared window (NIR-II, 1000-1700 nm). NIR-II light is particularly interesting for non-invasive, real-time imaging and diagnosis of living organisms, as it is unaffected by the native fluorescence of biological tissues and fluids, and can penetrate through them. In addition, multiplex imaging enables the simultaneous, real-time visualization of several biological markers for even more precise diagnosis of diseases and a deeper understanding of biological processes. This new family of molecular imaging agents is based on an innovative design and combines the exceptional advantages of “metallacrowns” to emit NIR-II light with those of ruthenium complexes, which exhibit strong absorption in the visible range and effectively sensitize lanthanides. Using NIR-II imaging experiments, we have been able to demonstrate that four bands from three different lanthanides can be distinguished unambiguously due to their minimal overlap, while exhibiting sufficient intensity to be detected through a tissue-mimicking phantom.

Enabling Visible Light Sensitization of YbIII, NdIII and ErIII in Dimeric LnIII/GaIII Metallacrowns through Functionalization with RuII Complexes for NIR-II Multiplex Imaging
Codruţa C. Bădescu-Singureanu, Dr. Anton S. Nizovtsev, Prof. Dr. Vincent L. Pecoraro, Prof. Dr. Stéphane Petoud, Dr. Svetlana V. Eliseeva
Angewandte Chemie International Edition 2024
https://doi-org.inc.bib.cnrs.fr/10.1002/anie.202416101

This article was reported by CNRS Chimie on its website.

A new regulatory mechanism involved in the bacterial response to cold shock

Cold shock is a common stress for bacterial pathogens inhabiting warm-blooded hosts. It occurs upon abrupt release from the host into the comparatively cold environment. Understanding how pathogens cope with cold shock is crucial to define how they survive on contaminated surfaces and spread to new hosts.

The‘RNA remodeling’ team and I2BC colleagues discovered that transcription termination factor Rho is a crucial player in the bacterial cold shock response (CSR), challenging the prevalent view that the CSR is mostly a posttranscriptional program. Temperature-sensing mRNA switches either allow (at 37°C) or prevent (at 15°C) Rho-dependent termination of the transcription of cold shock genes. During cold acclimation, the cold shock proteins accumulate until they bind to their mRNAs and switch them back into conformations prone to Rho action, thereby providing negative feedback control of their own expression. This regulatory loop works alongside the established posttanscriptional mechanisms to ensure tight and quick regulation of the cold shock genes.

This discovery published in the journal Molecular Cell illustrates the complexity of the bacterial stress responses and highlights Rho as a promising therapeutic target. It was reported by CNRS Chimie on its website.

Référence :
Rho-dependent transcriptional switches regulate the bacterial response to cold shock
Mildred Delaleau, Nara Figueroa-Bossi, Thuy Duong Do, Patricia Kerboriou, Eric Eveno, Lionello Bossi, & Marc Boudvillain*
Molecular Cell https://doi.org/10.1016/jmolcel.2024.07.034

Contrast agents to combine 1H and 19F MRI

Today, magnetic resonance imaging (MRI) is based on the detection of water protons (1H) in tissues. MRI of 19F fluorine offers complementary advantages, but its use is hampered by a lack of suitable imaging agents, soluble in water and easily detectable. In order to improve the sensitivity of detecting 19F MRI signals, a CBM team used Mn2+ ions to form complexes with small fluorinated molecules. Unlike currently used nanoparticles, these small molecular probes have well-defined chemical structures and better biocompatibility and water solubility. Finally, thanks to the paramagnetism of manganese(II), they generate a strong signal in MRI. In addition, these fluorinated contrast agents are also active in proton MRI, allowing proton and fluorine MRI images to be superimposed for precise anatomical mapping.

This advance, published in Angewandte Chemie International Edition, opens new horizons in fluorine MRI. It was reported by CNRS Chimie on its website.

Reference :
Small, Fluorinated Mn2+ Chelate as an Efficient 1H and 19F MRI Probe
Éva Tóth, Zoltán Garda, Frédéric Szeremeta, Océane Quin, Enikő Molnár, Balázs Váradi, Rudy Clémençon, Sandra Même, Chantal Pichon and Gyula Tircsó
Angewandte Chemie International Edition, 2024
DOI: 10.1002/anie.202410998