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Open Access Research article

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

Silke Bergmann1, Philippa M Beard2, Bastian Pasche1, Stefan Lienenklaus3, Siegfried Weiss3, Cormac G M Gahan4, Klaus Schughart15 and Andreas Lengeling2*

Author Affiliations

1 Department of Infection Genetics, Helmholtz Centre for Infection Research & University of Veterinary Medicine Hannover, Braunschweig D-38124, Germany

2 Infection and Immunity Division, The Roslin Institute and R(D)SVS, University of Edinburgh, Easter Bush Veterinary Campus, Edinburgh EH25 9RG, UK

3 Molecular Immunology, Helmholtz Centre for Infection Research, Braunschweig D-38124, Germany

4 Department of Microbiology and School of Pharmacy, Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland

5 University of Tennessee Health Science Center, Memphis, TN, USA

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BMC Microbiology 2013, 13:90  doi:10.1186/1471-2180-13-90

Published: 23 April 2013

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.