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Characterization of the Yersinia Autotransporter Proteins (Yaps) and Their Roles in the Pathogenesis of Y. pestis
Date of Award
Doctor of Philosophy (PhD)
Yersinia pestis CO92 has 12 open reading frames encoding putative conventional autotransporters (yaps), nine of which appear to produce functional proteins. This work provides evidence supporting the annotation of these genes as autotransporters by demonstrating that the Yaps localize to the cell surface in both E. coli and Y. pestis, and that a subset is processed by bacterial omptin proteases and released into the supernatant. Using mouse models of plague, we determined that all nine yap genes are transcribed in the lymph nodes during bubonic infection and in the lungs during pneumonic infection, suggesting a role for the Yaps during infection. Autotransporters have been implicated in the pathogenesis of numerous Gram–negative bacteria. We therefore evaluated the contribution of several yaps to the virulence of Y. pestis in mouse models of plague and found three that are important for Y. pestis virulence. The yapE gene is unique in that it is found not only in Y. pestis, but also in the related gastrointestinal pathogens Y. pseudotuberculosis and Y. enterocolitica. Deletion of yapE from Y. pestis results in decreased efficiency in lymph node colonization and disseminated spread during bubonic infection. YapE appears to function as an adhesin, as it facilitates adhesion to eukaryotic cells and bacterial auto–aggregation. yapK and yapJ are found in Y. pestis and share high sequence identity, but only yapK is found in Y. pseudotuberculosis, along with two homologs not found in Y. pestis (YPTB3285 and YPTB3286). Phylogenetic analysis indicates that members of this family cluster as either YapK–like (YapK, YPTB0365, YPTB3285) or YapJ–like (YapJ, YPTB3286), while sharing >96% amino acid identity in their C–termini and 58-72% in their N–termini. Deletion of all yapJ/yapK, homologous in Y. pseudotuberculosis does not seem to impact virulence in orogastric or systemic infection models, but yapK and yapJ make non–redundant contributions to systemic Y. pestis infection. Further work aims to elucidate the specific functions of the Yaps and clarify the contributions of these proteins to Y. pestis pathogenesis.
Chair and Committee
Virginia L Miller
Michael G Caparon, David A Hunstad, Gregory D Longmore, Mark J Miller
Lenz, Jonathan David, "Characterization of the Yersinia Autotransporter Proteins (Yaps) and Their Roles in the Pathogenesis of Y. pestis" (2012). Arts & Sciences Electronic Theses and Dissertations. 121.