Outer Membrane Protein X (Ail) Contributes to Yersinia pestis Virulence in Pneumonic Plague and Its Activity Is Dependent on the Lipopolysaccharide Core Length
| Autor: | Gregory A. Bohach, Carolyn J. Hovde, Scott A. Minnich, Andrzej J. Wojtowicz, Anna M. Kolodziejek, Harold N. Rohde, Darren R. Schnider |
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| Rok vydání: | 2010 |
| Předmět: |
Lipopolysaccharides
Pneumonic plague Virulence Factors Yersinia pestis media_common.quotation_subject Immunology Virulence Yersinia Microbiology Bacterial Adhesion Rats Sprague-Dawley Mice medicine Animals Internalization Sequence Deletion media_common Mice Inbred BALB C Plague biology Yersiniosis Gene Expression Regulation Bacterial medicine.disease biology.organism_classification Molecular Pathogenesis Enterobacteriaceae Rats Infectious Diseases Microscopy Electron Scanning Female Parasitology Bacterial outer membrane Bacterial Outer Membrane Proteins |
| Zdroj: | Infection and Immunity. 78:5233-5243 |
| ISSN: | 1098-5522 0019-9567 |
| DOI: | 10.1128/iai.00783-10 |
| Popis: | Yersinia pestis , the causative agent of plague, is one of the most virulent microorganisms known. The outer membrane protein X (OmpX) in Y. pestis KIM is required for efficient bacterial adherence to and internalization by cultured HEp-2 cells and confers resistance to human serum. Here, we tested the contribution of OmpX to disease progression in the fully virulent Y. pestis CO92 strain by engineering a deletion mutant and comparing its ability in mediating pneumonic plague to that of the wild type in two animal models. The deletion of OmpX delayed the time to death up to 48 h in a mouse model and completely attenuated virulence in a rat model of disease. All rats challenged with 1 × 10 8 CFU of the ompX mutant survived, compared to the 50% lethal dose (LD 50 ) of 1.2 × 10 3 CFU for the wild-type strain. Because murine serum is not bactericidal for the ompX mutant, the mechanism underlying the delay in time to death in mice was attributed to loss of adhesion/internalization properties but not serum resistance. The rat model, which is most similar to humans, highlighted the critical role of serum resistance in disease. To resolve conflicting evidence for the role of Y. pestis lipopolysaccharide (LPS) and OmpX in serum resistance, ompX was cloned into Escherichia coli D21 and three isogenic derivatives engineered to have progressively truncated LPS core saccharides. OmpX-mediated serum resistance, adhesiveness, and invasiveness, although dependent on LPS core length, displayed these functions in E. coli , independently of other Yersinia proteins and/or LPS. Also, autoaggregation was required for efficient OmpX-mediated adhesiveness and internalization but not serum resistance. |
| Databáze: | OpenAIRE |
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