Sigma B contributes to Listeria monocytogenes gastrointestinal infection but not to systemic spread in the guinea pig infection model

Contributions of the alternative sigma factor sigma(B) to Listeria monocytogenes infection were investigated using strains bearing null mutations in sigB, prfA, or inlA or in selected inlA or prfA promoter regions. The Delta P4(inlA) strain, which has a deletion in the sigma(B_)dependent P4(inlA) promoter, and the Delta sigB strain had significantly reduced invasion efficiencies relative to that of the wild-type strain in the Caco-2 human colorectal epithelial cell line, while the invasion efficiency of a strain bearing a deletion in the partially sigma(B) dependent P2(prf4) promoter region did not differ from that of the wild type. The virulence of the Delta sigB and Delta P4(inla) strains was attenuated in intragastrically inoculated guinea pigs, with the Delta sigB strain showing greater attenuation, while the virulence capacity of the AP2(prfA) strain was similar to that of the wild-type strain, suggesting that attenuation of virulence due to the Delta sigB mutation does not result from loss of sigma(B)-dependent prfA transcription. Our results show that sigma(B)-dependent activation of inlA is important for cell invasion and gastrointestinal infection and suggest that sigma(B)-regulated genes in addition to inlA appear to contribute to gastrointestinal infection. Interestingly, the virulence of the Delta sigB strain was not attenuated in intravenously infected guinea pigs. We conclude that (i) L. monocytogenes sigma(B) plays a critical role in invasion of human host cells, (ii) sigma(B_)mediated contributions to invasion are, in part, due to direct effects on inlA transcription but not on prfA transcription, and (iii) sigma(B) plays a critical role during the gastrointestinal stage of listeriosis in the guinea pig but is not important for systemic spread of the organism.