Lien vers Pubmed [PMID] – 31955655
Gut Microbes 2020 Jan;:1-14
The capacity of bacterial pathogens to infect their hosts depends on the tight spatiotemporal regulation of virulence genes. The () metal efflux pump repressor CadC is highly expressed during late infection stages, modulating lipoprotein processing and host immune response. Here we investigate the potential of CadC as broad repressor of virulence genes. We show that CadC represses the expression of the bile salt hydrolase impairing resistance to bile. During late infection, in absence of CadC-dependent repression, the constitutive bile salt hydrolase expression induces the overexpression of the cholic acid efflux pump MdrT that is unfavorable to virulence. We establish the CadC regulon and show that CadC represses additional virulence factors activated by σ during colonization of the intestinal lumen. CadC is thus a general repressor that promotes virulence by down-regulating, at late infection stages, genes required for survival in the gastrointestinal tract. This demonstrates for the first time how bacterial pathogens can repurpose regulators to spatiotemporally repress virulence genes and optimize their infectious capacity.