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

Abstract

<jats:title>Abstract</jats:title> <jats:sec> <jats:title>Background</jats:title> <jats:p>The bacterial surface protein internalin (InlA) is a major virulence factor of the food-born pathogen <jats:italic>Listeria monocytogenes</jats:italic>. 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 <jats:italic>Listeria</jats:italic> strains to examine the spatiotemporal dissemination of <jats:italic>Listeria</jats:italic> in four diverse mouse genetic backgrounds after oral inoculation.</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>The murinised <jats:italic>Listeria monocytogenes</jats:italic> strain showed enhanced invasiveness and induced more severe infections in all four investigated mouse inbred strains compared to the non-murinised <jats:italic>Listeria</jats:italic> 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 <jats:italic>Listeria</jats:italic> dissemination, higher bacterial loads in internal organs, and elevated serum levels of IL-6, IFN-?, TNF-a and CCL2 in the susceptible strains as compared to the resistant C57BL/6J strain. Importantly, murinisation of InlA did not cause enhanced invasion of <jats:italic>Listeria monocytogenes</jats:italic> into the brain.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusion</jats:title> <jats:p>Murinised <jats:italic>Listeria</jats:italic> 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 <jats:italic>Listeria monocytogenes</jats:italic> through different molecular mechanisms.</jats:p> </jats:sec>