title: Impact of the Listeria monocytogenes protein InlC on infection in mice.
abstract: The bacterial pathogen Listeria monocytogenes causes serious food-borne illnesses in pregnant women and the immunocompromised. L. monocytogenes promotes its internalization into host epithelial cells and then uses an F-actin-dependent motility process to spread from infected cells to surrounding healthy cells. In cultured enterocytes, efficient spread of L. monocytogenes requires the secreted bacterial protein InlC. InlC promotes dissemination by physically interacting with and antagonizing the function of the human adaptor protein Tuba. Here we examine the role of InlC and its interaction with host Tuba during infection in mice. The study took advantage of a single-amino-acid substitution (K173A) in InlC that impairs binding to human Tuba but does not affect InlC-mediated inhibition of the NF-κB pathway. Mice were inoculated intravenously with the wild-type L. monocytogenes strain EGD, an isogenic strain deleted for the inlC gene (ΔinlC), or a strain expressing K173A mutant InlC (inlC.K173A). The 50% lethal doses (LD(50)) for the ΔinlC or inlC.K173A mutant strain were approximately 4- or 6-fold greater than that for the wild-type strain, indicating a role for inlC in virulence. Compared to the wild-type strain, the inlC.K173A mutant strain exhibited lower bacterial loads in the liver. Histological analysis of livers indicated that the two inlC mutant strains produced smaller foci of infection than did the wild-type strain. These smaller foci are consistent with a role for InlC in cell-to-cell spread in vivo. Taken together, these results provide evidence that interaction of InlC with host Tuba is important for full virulence.
authors: Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
authors: Nelly
authors: N
authors: Leung
authors: Antonella
authors: A
authors: Gianfelice
authors: Scott D
authors: SD
authors: Gray-Owen
authors: Keith
authors: K
authors: Ireton
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D058491:Bacterial Load; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D017353:Gene Deletion; D006651:Histocytochemistry; D054884:Host-Pathogen Interactions; D007928:Lethal Dose 50; D008089:Listeria monocytogenes / Q000235:genetics / Q000472:pathogenicity*; D008088:Listeriosis / Q000382:microbiology* / Q000473:pathology*; D008099:Liver / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism; D020125:Mutation, Missense; D011485:Protein Binding; D016019:Survival Analysis; D014404:Tubulin / Q000378:metabolism*; D037521:Virulence Factors / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D050505:Mutant Proteins; C569741:Tuba1a protein, mouse; D014404:Tubulin; D037521:Virulence Factors; C103178:inlC protein, Listeria monocytogenes
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