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Infection and Immunity, February 2010, p. 773-782, Vol. 78, No. 2
0019-9567/10/$12.00+0     doi:10.1128/IAI.00718-09
Copyright © 2010, American Society for Microbiology. All Rights Reserved.

Yersinia pestis Two-Component Gene Regulatory Systems Promote Survival in Human Neutrophils{triangledown}

Jason L. O'Loughlin, Justin L. Spinner, Scott A. Minnich, and Scott D. Kobayashi*

Department of Microbiology, Molecular Biology, and Biochemistry, University of Idaho, 222 Ag Biotech, Moscow, Idaho 83844

Received 25 June 2009/ Returned for modification 5 August 2009/ Accepted 15 November 2009

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 as Yersinia pestis resist destruction by the innate immune system and are able to survive in macrophages and neutrophils. The specific molecular mechanisms used by Y. pestis to survive following phagocytosis by human PMNs are incompletely defined. To gain insight into factors that govern Y. pestis intracellular 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. pestis strains 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, only Y. pestis {Delta}phoPQ demonstrated global sensitivity to a panel of seven individual neutrophil antimicrobial peptides and serine proteases. Notably, Y. pestis {Delta}phoPQ was deficient for intracellular survival in PMNs. Iterative analysis with Y. pestis strains lacking the PhoP-regulated genes ugd and pmrK indicated 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 about Y. pestis evasion of the innate immune system.

* Corresponding author. Present address: Laboratory of Human Bacterial Pathogenesis, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 903 South 4th Street, Hamilton, MT 59840. Phone: (406) 375-9704. Fax: (406) 363-9394. E-mail: kobayashis{at}niaid.nih.gov

{triangledown} Published ahead of print on 23 November 2009.

Editor: J. B. Bliska

Infection and Immunity, February 2010, p. 773-782, Vol. 78, No. 2
0019-9567/10/$12.00+0     doi:10.1128/IAI.00718-09
Copyright © 2010, American Society for Microbiology. All Rights Reserved.





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