Three Yersinia pestis Adhesins Facilitate Yop Delivery to Eukaryotic Cells and Contribute to Plague Virulence
- 1 October 2010
- journal article
- Published by American Society for Microbiology in Infection and Immunity
- Vol. 78 (10), 4134-4150
- https://doi.org/10.1128/iai.00167-10
Abstract
To establish a successful infection, Yersinia pestis requires the delivery of cytotoxic Yops to host cells. Yops inhibit phagocytosis, block cytokine responses, and induce apoptosis of macrophages. The Y. pestis adhesin Ail facilitates Yop translocation and is required for full virulence in mice. To determine the contributions of other adhesins to Yop delivery, we deleted five known adhesins of Y. pestis . In addition to Ail, plasminogen activator (Pla) and pH 6 antigen (Psa) could mediate Yop translocation to host cells. The contribution of each adhesin to binding and Yop delivery was dependent upon the growth conditions. When cells were pregrown at 28°C and pH 7, the order of importance for adhesins in cell binding and cytotoxicity was Ail > Pla > Psa. Y. pestis grown at 37°C and pH 7 had equal contributions from Ail and Pla but an undetectable role for Psa. At 37°C and pH 6, both Ail and Psa contributed to binding and Yop delivery, while Pla contributed minimally. Pla-mediated Yop translocation was independent of protease activity. Of the three single mutants, the Δ ail mutant was the most defective in mouse virulence. The expression level of ail was also the highest of the three adhesins in infected mouse tissues. Compared to an ail mutant, additional deletion of psaA (encoding Psa) led to a 130,000-fold increase in the 50% lethal dose for mice relative to that of the KIM5 parental strain. Our results indicate that in addition to Ail, Pla and Psa can serve as environmentally specific adhesins to facilitate Yop secretion, a critical virulence function of Y. pestis .Keywords
This publication has 67 references indexed in Scilit:
- Ail Binding to Fibronectin Facilitates Yersinia pestis Binding to Host Cells and Yop DeliveryInfection and Immunity, 2010
- TheYersinia pestisAil Protein Mediates Binding and Yop Delivery to Host Cells Required for Plague VirulenceInfection and Immunity, 2009
- Plasminogen Activator Pla of Yersinia pestis Utilizes Murine DEC-205 (CD205) as a Receptor to Promote DisseminationJournal of Biological Chemistry, 2008
- Characterization of Complement Factor H Binding toYersinia enterocoliticaSerotype O:3Infection and Immunity, 2008
- Resistance of Yersinia pestis to Complement-Dependent Killing Is Mediated by the Ail Outer Membrane ProteinInfection and Immunity, 2008
- Plague: Past, Present, and FuturePLoS Medicine, 2008
- Yersinia Controls Type III Effector Delivery into Host Cells by Modulating Rho ActivityPLoS Pathogens, 2008
- The Psa Fimbriae of Yersinia pestis Interact with Phosphatidylcholine on Alveolar Epithelial Cells and Pulmonary SurfactantInfection and Immunity, 2007
- RovA, a global regulator of Yersinia pestis , specifically required for bubonic plagueProceedings of the National Academy of Sciences, 2006
- Genome sequence of Yersinia pestis, the causative agent of plagueNature, 2001