Yersinia pestis and

The transcriptional activator PhoP is important for survival of Yersinia pestis in macrophage phagosomes. However, the phagosomes inhabited by Y. pestis have not been well characterized, and the mechanism by which PhoP promotes bacterial survival in these vacuoles is not fully understood. Lysosomal tracers, as well as antibodies to late endosomal or lysosomal proteins, were used in conjunction with confocal or electron microscopy to study the trafficking of phagosomes containing phoP

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-␥. Y. pestis was able to replicate in macrophages that were activated with IFN-␥ 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 ⌬pgm replicated in iNOS ؊/؊ macrophages that were postactivated with IFN-␥, suggesting that killing of ⌬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-␥ and identify a potential virulence gene encoded in the pgm locus that is required for this activity.intracellular replication ͉ nitric oxide