Replication of Yersinia pestis in interferon gamma-activated macrophages requires ripA, a gene encoded in the pigmentation locus.
Yersinia pestis is a facultative intracellular bacterial pathogen that can replicate in macrophages. Little is known about the mechanism by which Y. pestis replicates in macrophages, and macrophage defense mechanisms important for limiting intracellular survival of Y. pestis have not been characterized. In this work, we investigated the ability of Y. pestis to replicate in primary murine macrophages that were activated with IFN-gamma. Y. pestis was able to replicate in macrophages that were activated with IFN-gamma after infection (postactivated). A region of chromosomal DNA known as the pigmentation (pgm) locus was required for replication in postactivated macrophages, and this replication was associated with reduced nitric oxide (NO) levels but not with reduced inducible NO synthase (iNOS) expression. Y. pestis delta pgm replicated in iNOS-/- macrophages that were postactivated with IFN-gamma, suggesting that killing of delta pgm Y. pestis is NO-dependent. A specific genetic locus within pgm, which shares similarity to a pathogenicity island in Salmonella, was shown to be required for replication of Y. pestis and restriction of NO levels in postactivated macrophages. These data demonstrate that intracellular Y. pestis can evade killing by macrophages that are exposed to IFN-gamma and identify a potential virulence gene encoded in the pgm locus that is required for this activity.
Pujol
Céline
C
Department of Molecular Genetics and Microbiology and Center for Infectious Diseases, State University of New York, Stony Brook, NY 11794-5222, USA.
Grabenstein
Jens P
JP
Perry
Robert D
RD
Bliska
James B
JB
D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000235:genetics; D005260:Female; D005798:Genes, Bacterial / Q000235:genetics; D007371:Interferon-gamma / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects* / Q000382:microbiology*; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism; D010858:Pigmentation / Q000235:genetics*; D014774:Virulence / Q000235:genetics; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism; D015010:Yersinia pestis / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism* / Q000472:pathogenicity
D001426:Bacterial Proteins; D037521:Virulence Factors; D009569:Nitric Oxide; D007371:Interferon-gamma