Impact of the Listeria monocytogenes protein InlC on infection in mice. Infect. Immun. 81, 1334–1340. doi

The bacterial pathogen Listeria monocytogenes causes serious food-borne illnesses in pregnant women and the immunocompro-mised. L. monocytogenes promotes its internalization into host epithelial cells and then uses an F-actin-dependent motility pro-cess to spread from infected cells to surrounding healthy cells. In cultured enterocytes, efficient spread of L. monocytogenes re-quires 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 infec-tion 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-B pathway. Mice were inoculated intravenously with the wild-type L. monocytogenes strain EGD, an isogenic strain deleted for the inlC gene (inlC), or a strain expressing K173Amutant InlC (inlC.K173A). The 50 % lethal doses (LD50) for theinlC or inlC.K173Amutant 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.K173Amu-tant strain exhibited lower bacterial loads in the liver. Histological analysis of livers indicated that the two inlCmutant 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. Listeria monocytogenes is a food-borne, intracellular pathogenthat causes gastroenteritis, abortions, or meningitis with a hig