Deletion of <i>rgaS</i> reduces virulence in a mouse model of <i>Clostridioides difficile</i> infection

Highlights<br></br> • The gene encoding histidine kinase r<i>gaS</i> (R20291_0503) was deleted in <i>C. difficile</i> R20291.<br></br> • Cytotoxicity towards Vero cells was reduced for the <i>rgaS</i> mutant signifying a reduction in TcdA and TcdB in the supernatant.<br></br> • Western blot analysis revealed a reduction in the amount of CDT in the supernatant of the r<i>gaS</i> mutant.<br></br> • The mutant was less virulent in a mouse model of <i>C. difficile</i> infection, compared with the wildtype parental.<br></br> • These data demonstrate the contribution of RgaS to <i>C. difficile</i> virulence.<br></br><br></br> Abstract<br></br> Two-component system signalling is involved in several processes relevant to <i>Clostridioides difficile</i> virulence. We demonstrate that deletion of the orphan histidine kinase rgaS (R20291_0503), reduces detectable toxin in the supernatant of R20291 and impairs virulence in a mouse model of infection. These data suggest that RgaS regulates virulence capabilities in hypervirulent <i>C. difficile</i>.