Evolution and Virulence Contributions of the Autotransporter Proteins YapJ and YapK of Yersinia pestisCO92 and Their Homologs in Y. pseudotuberculosisIP32953

ABSTRACTYersinia pestis, the causative agent of plague, evolved from the gastrointestinal pathogen Yersinia pseudotuberculosis. Both species have numerous type Va autotransporters, most of which appear to be highly conserved. In Y. pestisCO92, the autotransporter genes yapKand yapJshare a high level of sequence identity. By comparing yapKand yapJto three homologous genes in Y. pseudotuberculosisIP32953 (YPTB0365, YPTB3285, and YPTB3286), we show that yapKis conserved in Y. pseudotuberculosis, while yapJis unique to Y. pestis. All of these autotransporters exhibit >96% identity in the C terminus of the protein and identities ranging from 58 to 72% in their N termini. By extending this analysis to include homologous sequences from numerous Y. pestisand Y. pseudotuberculosisstrains, we determined that these autotransporters cluster into a YapK (YPTB3285) class and a YapJ (YPTB3286) class. The YPTB3286-like gene of most Y. pestisstrains appears to be inactivated, perhaps in favor of maintaining yapJ. Since autotransporters are important for virulence in many bacterial pathogens, including Y. pestis, any change in autotransporter content should be considered for its impact on virulence. Using established mouse models of Y. pestisinfection, we demonstrated that despite the high level of sequence identity, yapKis distinct from yapJin its contribution to disseminated Y. pestisinfection. In addition, a mutant lacking both of these genes exhibits an additive attenuation, suggesting nonredundant roles for yapJand yapKin systemic Y. pestisinfection. However, the deletion of the homologous genes in Y. pseudotuberculosisdoes not seem to impact the virulence of this organism in orogastric or systemic infection models.