Yersinia pestis Two-Component Gene Regulatory Systems Promote Survival in Human Neutrophils▿
| Autor: | Justin L. Spinner, Scott A. Minnich, Scott D. Kobayashi, Jason L. O'Loughlin |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
Proteases
Innate immune system Neutrophils Reverse Transcriptase Polymerase Chain Reaction Yersinia pestis Phagocytosis Immunology Antimicrobial peptides Biology biology.organism_classification Microbiology Enterobacteriaceae Molecular Pathogenesis Infectious Diseases Immunity Genes Bacterial Humans Parasitology Intracellular Immune Evasion |
| Popis: | Human polymorphonuclear leukocytes (PMNs, or neutrophils) are the most abundant innate immune cell and kill most invading bacteria through combined activities of reactive oxygen species (ROS) and antimicrobial granule constituents. Pathogens such asYersinia pestisresist destruction by the innate immune system and are able to survive in macrophages and neutrophils. The specific molecular mechanisms used byY. pestisto survive following phagocytosis by human PMNs are incompletely defined. To gain insight into factors that governY. pestisintracellular survival in neutrophils, we inactivated 25 two-component gene regulatory systems (TCSs) with known or inferred function and assessed susceptibility of these mutant strains to human PMN granule extracts.Y. pestisstrains deficient for PhoPQ, KdpED, CheY, CvgSY, and CpxRA TCSs were selected for further analysis, and all five strains were altered for survival following interaction with PMNs. Of these five strains, onlyY. pestisΔphoPQdemonstrated global sensitivity to a panel of seven individual neutrophil antimicrobial peptides and serine proteases. Notably,Y. pestisΔphoPQwas deficient for intracellular survival in PMNs. Iterative analysis withY. pestisstrains lacking the PhoP-regulated genesugdandpmrKindicated that the mechanism most likely responsible for increased resistance to killing is 4-amino-4-deoxy-l-arabinose modification of lipid A. Together, the data provide new information aboutY. pestisevasion of the innate immune system. |
| Databáze: | OpenAIRE |
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