Control of bacterial virulence by transcription factors NusG and Rho

14 October 2019 par Isabelle Frapart
Scientists from I2BC (CNRS, Gif-sur-Yvette) and CBM uncover the pivotal role of transcription factors NusG and Rho in the silencing of the pathogenicity islands of Salmonella enterica.

The virulence genes of pathogenic enterobacteria are concentrated in genomic islands acquired by horizontal transfer during evolution. The expression of these genes outside the infection phase is detrimental to the bacterium and is therefore highly regulated. A major regulatory mechanism relies on the histone-like protein H-NS, which binds to AT-rich sites characteristic of horizontally acquired DNA and forms oligomeric structures that inhibit transcription over extended regions. These regions, however, remain exposed to invasive transcription from neighboring regions or to H-NS repression defects. Our data support a model in which the transcription elongation factor NusG “secures” the inhibition of virulence genes by stimulating the activity of the transcription termination factor Rho in regions silenced by H-NS. Remarkably, NusG changes the specificity of the Rho factor, which alone preferentially targets C-rich regions. The perturbation of this NusG/Rho-dependent mechanism in Salmonella has profound physiological consequences, probably because unstopped transcription in H-NS -targeted regions feeds a feed-forward activation cascade leading to the uncontrolled expression of pathogenicity islands and co-regulated loci.

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