Clostridium difficile Extracytoplasmic Function σ Factor σ V Regulates Lysozyme Resistance and Is Necessary for Pathogenesis in the Hamster Model of Infection

Abstract

ABSTRACT Clostridium difficile is a clinically important pathogen and the most common cause of hospital-acquired infectious diarrhea. Expression of the C. difficile gene csfV , which encodes σ V , an extracytoplasmic function σ factor, is induced by lysozyme, which damages the peptidoglycan of bacteria. Here we show that σ V is required for lysozyme resistance in C. difficile . Using microarray analysis, we identified the C. difficile genes whose expression is dependent upon σ V and is induced by lysozyme. Although the peptidoglycan of wild-type C. difficile is intrinsically highly deacetylated, we have found that exposure to lysozyme leads to additional peptidoglycan deacetylation. This lysozyme-induced deacetylation is dependent upon σ V . Expression of pdaV , which encodes a putative peptidoglycan deacetylase, was able to increase lysozyme resistance of a csfV mutant. The csfV mutant strain is severely attenuated compared to wild-type C. difficile in a hamster model of C. difficile -associated disease. We conclude that the σ V signal transduction system, which senses the host innate immune defense enzyme lysozyme, is required for lysozyme resistance and is necessary during C. difficile infection.