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Sigma B Contributes to Listeria monocytogenes Gastrointestinal Infection but Not to Systemic Spread in the Guinea Pig Infection Model

Garner, M. R., Njaa, B. L., Wiedmann, M., Boor, K. J.
Infection and immunity 2006 v.74 no.2 pp. 876-886
Listeria monocytogenes, cell invasion, epithelial cells, gastrointestinal system, genes, guinea pigs, humans, intravenous injection, listeriosis, models, mutation, promoter regions, virulence
Contributions of the alternative sigma factor [sigma][superscript 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[subscript inlA] strain, which has a deletion in the [sigma][superscript B]-dependent P4[subscript 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][superscript B] dependent P2[subscript prfA] promoter region did not differ from that of the wild type. The virulence of the [Delta]sigB and [Delta]P4[subscript inlA] strains was attenuated in intragastrically inoculated guinea pigs, with the [Delta]sigB strain showing greater attenuation, while the virulence capacity of the [Delta]P2[subscript 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][superscript B]-dependent prfA transcription. Our results show that [sigma][superscript B]-dependent activation of inlA is important for cell invasion and gastrointestinal infection and suggest that [sigma][superscript 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][superscript B] plays a critical role in invasion of human host cells, (ii) [sigma][superscript B]-mediated contributions to invasion are, in part, due to direct effects on inlA transcription but not on prfA transcription, and (iii) [sigma][superscript 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.