Carbon storage regulator CsrA plays important roles in multiple virulence-associated processes of Clostridium difficile

Abstract

The carbon storage regulator CsrA is a global regulator that controls multiple virulence-associated processes including host cell invasion, virulence secretion, quorum sensing, biofilm formation, and motility in many pathogenic bacteria. However, the roles of CsrA in Clostridium difficile still remain unclear. In this study, a C. difficile strain overexpressing csrA was constructed to investigate its effects on multiple virulence associated processes. Overexpression of csrA resulted in flagella defect and poor motility in C. difficile 630Δerm, suggesting that CsrA involves in the regulation of flagellum synthesis. The levels of toxin production were increased in the C. difficile 630Δerm overexpressing of csrA. Moreover, csrA overexpression enhanced the adherence ability to Caco-2 cells and solvent production of C. difficile 630Δerm. Altogether, CsrA of C. difficile participates in multiple virulence processes including toxin production, motility, and adherence, and in the regulation of carbon metabolism. These results enhance our understanding of the regulatory functions of CsrA and reveal that CsrA is an important regulator in C. difficile contributing to virulence regulation.