The antivirulent Staphylococcal sRNA SprC regulates CzrB efflux pump to adapt its response to Zinc toxicity

Bacterial regulatory RNAs (sRNAs) are important players to control gene expression. In S. aureus , SprC is an antivirulent trans -acting sRNA known to base-pair with the major autolysin atl mRNA, preventing its translation. Using MS2-affinity purification coupled with RNA sequencing (MAPS), we looked for its sRNA-RNA interactome and identified fourteen novel mRNA targets. In vitro biochemical investigations revealed that SprC binds two of them, czrB and deoD , and uses a single accessible region to regulate its targets, including Atl translation. Unlike Atl regulation, the characterization of the SprC- czrB interaction pinpointed a destabilization of czrAB co-transcript,leading to a decrease of the mRNA level that impaired CzrB Zinc efflux pump expression. On a physiological stand-point, we showed that SprC expression is detrimental to combat against Zinc toxicity. In addition, phagocyctosis assays revealed a significant, but moderate, increase of czrB mRNA level in a sprC -deleted mutant, indicating a functional link between SprC and czrB upon internalization in macrophages, and suggesting a role in resistance to both oxidative and Zinc burst. Altogether, our data uncover a novel pathway in which SprC is implicated, highlighting the multiple strategies employed by S. aureus to balance virulence using an RNA regulator.