Superantigen YPMa Exacerbates the Virulence ofYersinia pseudotuberculosisin Mice

Abstract
Yersinia pseudotuberculosis, a gram-negative bacterium responsible for enteric and systemic infection in humans, produces a superantigenic toxin designated YPMa (Y. pseudotuberculosis-derived mitogen). To assess the role of YPMa in the pathogenesis ofY. pseudotuberculosis, we constructed a superantigen-deficient mutant and compared its virulence in a mouse model of infection to the virulence of the wild-type strain. Determination of the survival rate after intravenous (i.v.) bacterial inoculation of OF1 mice clearly showed that inactivation ofypmA, encoding YPMa, reduced the virulence ofY. pseudotuberculosis. Mice infected i.v. with 104and 105wild-type bacteria died within 9 days, whereas mice infected with theypmAmutant survived 12 and 3 days longer, respectively. This decreased virulence of theypmAmutant strain was not due to an impaired colonization of the spleen, liver, or lungs. In contrast to i.v. challenge, bacterial inoculation by the intragastric (i.g.) route did not reveal any difference in virulence between wild-typeY. pseudotuberculosisand theypmAmutant since the 50% lethal doses were identical for both strains. Moreover, inactivation ofypmAgene did not affect the bacterial growth ofY. pseudotuberculosisin Peyer's patches, mesenteric lymph nodes (MLNs), and spleen after oral infection. Histological studies of spleen, liver, lungs, heart, Peyer's patches, and MLNs after i.v. or i.g. challenge with the wild type or theypmAmutant did not reveal any feature that can be specifically related to YPMa. Our data show that the superantigenic toxin YPMa contributes to the virulence ofY. pseudotuberculosisin systemic infection in mice.