Superantigen YPMa exacerbates the virulence of Yersinia pseudotuberculosisin mice

Yersinia pseudotuberculosis, a gram-negative bacterium responsible for ente ric and systemic infection in humans, produces a superantigenic toxin desig nated YPMa (Y. pseudotuberculosis-derived mitogen). To assess the role of Y PMa in the pathogenesis of Y. pseudotuberculosis, we constructed a superant igen-deficient mutant and compared its virulence in a mouse model of infect ion to the virulence of the wild-type strain. Determination of the survival rate after intravenous (i.v.) bacterial inoculation of OF1 mice clearly sh owed that inactivation of ypmA, encoding YPMa, reduced the virulence of Y. pseudotuberculosis. Mice infected i.v. with 10(4) and 10(5) wild-type bacte ria died within 9 days, whereas mice infected with the ypmA mutant survived 12 and 3 days longer, respectively. This decreased virulence of the ypmA m utant strain was not due to an impaired colonization of the spleen, liver, or lungs. In contrast to i.v. challenge, bacterial inoculation by the intra gastric (i.g.) route did not reveal any difference in virulence between wil d-type Y. pseudotuberculosis and the ypmA mutant since the 50% lethal doses were identical for both strains. Moreover, inactivation of ypmA gene did n ot affect the bacterial growth of Y. pseudotuberculosis in Peyer's patches, mesenteric lymph nodes (MLNs), and spleen after oral infection. Histologic al studies of spleen, liver, lungs, heart, Peyer's patches, and MLNs after i.v. or i.g. challenge with the wild type or the ypmA mutant did not reveal any feature that can be specifically related to YPMa. Our data show that t he superantigenic toxin YPMa contributes to the virulence of Y. pseudotuber culosis in systemic infection in mice.