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

Abstract

Contributions of the alternative sigma factor sigmaB 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 DeltaP4inlA strain, which has a deletion in the sigmaB-dependent P4inlA promoter, and the DeltasigB 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 sigmaB dependent P2prfA promoter region did not differ from that of the wild type. The virulence of the DeltasigB and DeltaP4inlA strains was attenuated in intragastrically inoculated guinea pigs, with the DeltasigB strain showing greater attenuation, while the virulence capacity of the DeltaP2prfA strain was similar to that of the wild-type strain, suggesting that attenuation of virulence due to the DeltasigB mutation does not result from loss of sigmaB-dependent prfA transcription. Our results show that sigmaB-dependent activation of inlA is important for cell invasion and gastrointestinal infection and suggest that sigmaB-regulated genes in addition to inlA appear to contribute to gastrointestinal infection. Interestingly, the virulence of the DeltasigB strain was not attenuated in intravenously infected guinea pigs. We conclude that (i) L. monocytogenes sigmaB plays a critical role in invasion of human host cells, (ii) sigmaB-mediated contributions to invasion are, in part, due to direct effects on inlA transcription but not on prfA transcription, and (iii) sigmaB plays a critical role during the gastrointestinal stage of listeriosis in the guinea pig but is not important for systemic spread of the organism.