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

Author:
Garner, M. R., Njaa, B. L., Wiedmann, M., Boor, K. J.
Source:
Infection and immunity 2006 v.74 no.2 pp. 876-886
ISSN:
0019-9567
Subject:
Listeria monocytogenes, cell invasion, epithelial cells, gastrointestinal system, genes, guinea pigs, humans, intravenous injection, listeriosis, models, mutation, promoter regions, virulence
Abstract:
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.
Agid:
267357