Influence of internalin a murinisation on host resistance to orally acquired listeriosis in mice

dc.contributor.authorBergmann, Silke
dc.contributor.authorBeard, Philippa M.
dc.contributor.authorPasche, Bastian
dc.contributor.authorLienenklaus, Stefan
dc.contributor.authorWeiss, Siegfried
dc.contributor.authorGahan, Cormac G.en
dc.contributor.authorSchughart, Klaus
dc.contributor.authorLengeling, Andreas
dc.contributor.funderNational German Genome Network
dc.contributor.funderEuropean Commission
dc.contributor.funderBiotechnology and Biological Sciences Research Council
dc.contributor.funderHelmholtz Centre for Infection Research, Germany
dc.date.accessioned2016-02-25T17:20:02Z
dc.date.available2016-02-25T17:20:02Z
dc.date.issued2013-04-23
dc.description.abstractBackground: The bacterial surface protein internalin (InlA) is a major virulence factor of the food-born pathogen Listeria monocytogenes. It plays a critical role in the bacteria crossing the host intestinal barrier by a species-specific interaction with the cell adhesion molecule E-cadherin. In mice, the interaction of InlA with murine E-cadherin is impaired due to sequence-specific binding incompatibilities. We have previously used the approach of ‘murinisation’ to establish an oral listeriosis infection model in mice by exchanging two amino acid residues in InlA. This dramatically increases binding to mouse E-cadherin. In the present study, we have used bioluminescent murinised and non-murinised Listeria strains to examine the spatiotemporal dissemination of Listeria in four diverse mouse genetic backgrounds after oral inoculation. Results: The murinised Listeria monocytogenes strain showed enhanced invasiveness and induced more severe infections in all four investigated mouse inbred strains compared to the non-murinised Listeria strain. We identified C57BL/6J mice as being most resistant to orally acquired listeriosis whereas C3HeB/FeJ, A/J and BALB/cJ mice were found to be most susceptible to infection. This was reflected in faster kinetics of Listeria dissemination, higher bacterial loads in internal organs, and elevated serum levels of IL-6, IFN-γ, TNF-α and CCL2 in the susceptible strains as compared to the resistant C57BL/6J strain. Importantly, murinisation of InlA did not cause enhanced invasion of Listeria monocytogenes into the brain. Conclusion: Murinised Listeria are able to efficiently cross the intestinal barrier in mice from diverse genetic backgrounds. However, expression of murinized InlA does not enhance listerial brain invasion suggesting that crossing of the blood brain barrier and crossing of the intestinal epithelium are achieved by Listeria monocytogenes through different molecular mechanisms.en
dc.description.sponsorshipNational German Genome Network (NGFN-Plus Grant Number 01GS0855); European Commission (EUMODIC Project - Framework Programme 6: LSHG-CT-2006-037188; European COST Action ‘SYSGENET’ BM901); Biotechnology and Biological Sciences Research Council, United Kingdom (Institute Strategic Grant); Helmholtz Centre for Infection Research (HZI), Germany (Institute Strategic Grant)en
dc.description.statusPeer revieweden
dc.description.versionPublished Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.articleid90
dc.identifier.citationBERGMANN, S., BEARD, P. M., PASCHE, B., LIENENKLAUS, S., WEISS, S., GAHAN, C. G. M., SCHUGHART, K. & LENGELING, A. 2013. Influence of internalin a murinisation on host resistance to orally acquired listeriosis in mice. BMC Microbiology, 13:90, 1-16. http://dx.doi.org/10.1186/1471-2180-13-90en
dc.identifier.doi10.1186/1471-2180-13-90
dc.identifier.endpage16en
dc.identifier.issn1471-2180
dc.identifier.journaltitleBMC Microbiologyen
dc.identifier.startpage1en
dc.identifier.urihttps://hdl.handle.net/10468/2403
dc.identifier.volume13en
dc.language.isoenen
dc.publisherBioMed Central Ltd.en
dc.rights© Bergmann et al.; licensee BioMed Central Ltd. 2013. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://​creativecommons.​org/​licenses/​by/​2.​0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.en
dc.rights.urihttp://​creativecommons.​org/​licenses/​by/​2.​0en
dc.subjectCentral nervous systemen
dc.subjectI interferon receptoren
dc.subjectMonocytogenes infectionen
dc.subjectE-cadherinen
dc.subjectGenetic controlen
dc.subjectSalmonella Typhimuriumen
dc.subjectBacterial infectionen
dc.subjectIntestinal barrieren
dc.subjectSurface proteinen
dc.subjectInnate immunityen
dc.subject~Microbiology - Journal Articles~en
dc.subject~Pharmacy - Journal Articles~en
dc.titleInfluence of internalin a murinisation on host resistance to orally acquired listeriosis in miceen
dc.typeArticle (peer-reviewed)en
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