2.50
Hdl Handle:
http://hdl.handle.net/10033/620706
Title:
Influence of internalin a murinisation on host resistance to orally acquired listeriosis in mice
Authors:
Bergmann, Silke; Beard, Philippa M; Pasche, Bastian; Lienenklaus, Stefan; Weiss, Siegfried; Gahan, Cormac G M; Schughart, Klaus; Lengeling, Andreas
Abstract:
Abstract Background 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.
Citation:
BMC Microbiology. 2013 Apr 23;13(1):90
Issue Date:
23-Apr-2013
URI:
http://dx.doi.org/10.1186/1471-2180-13-90; http://hdl.handle.net/10033/620706
Type:
Journal Article
Appears in Collections:
publications of the department infection genetics (INFG); publications of the service unit animal experimentation: (TEE)

Full metadata record

DC FieldValue Language
dc.contributor.authorBergmann, Silkeen
dc.contributor.authorBeard, Philippa Men
dc.contributor.authorPasche, Bastianen
dc.contributor.authorLienenklaus, Stefanen
dc.contributor.authorWeiss, Siegfrieden
dc.contributor.authorGahan, Cormac G Men
dc.contributor.authorSchughart, Klausen
dc.contributor.authorLengeling, Andreasen
dc.date.accessioned2017-01-16T15:29:09Z-
dc.date.available2017-01-16T15:29:09Z-
dc.date.issued2013-04-23en
dc.identifier.citationBMC Microbiology. 2013 Apr 23;13(1):90en
dc.identifier.urihttp://dx.doi.org/10.1186/1471-2180-13-90en
dc.identifier.urihttp://hdl.handle.net/10033/620706-
dc.description.abstractAbstract Background 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.titleInfluence of internalin a murinisation on host resistance to orally acquired listeriosis in miceen
dc.typeJournal Articleen
dc.language.rfc3066enen
dc.rights.holderBergmann et al.; licensee BioMed Central Ltd.en
dc.date.updated2015-09-04T08:30:11Zen
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