Role of Tellurite Resistance Operon in Filamentous Growth of Yersinia pestis in Macrophages

• Published in: PloS one 2015-11, Vol.10 (11), p.e0141984-e0141984
• Main Authors: Ponnusamy, Duraisamy, Clinkenbeard, Kenneth D
• Format: Article
• Language: English
• Subjects: Animals; Bacteria; Bacterial Proteins - genetics; Cell culture; Cell division; Cells, Cultured; Clonal deletion; Complementation; Cytology; Deletion mutant; Drug Resistance, Bacterial - genetics; E coli; Escherichia coli; Gene expression; Gene Expression Regulation, Bacterial; Genes; Genetic aspects; Genetic Complementation Test; Health sciences; Immune response; Immunity, Innate - genetics; Infections; Innate immunity; Intracellular; Kinases; Lymphatic system; Macrophages; Macrophages - microbiology; Mice; Morphology; Mycobacterium tuberculosis; Neutrophils; Operon - genetics; Oxidative stress; Parasitism; Pathogens; Phenotypes; Plague - drug therapy; Plague - genetics; Plague - microbiology; Proteins; Siphonaptera; Sodium; Sodium tellurite; Streptococcus infections; Stress response; Tellurite; Tellurium - pharmacology; Tellurium dioxide; Tuberculosis; Virulence - genetics; Yersinia; Yersinia pestis; Yersinia pestis - drug effects; Yersinia pestis - pathogenicity
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0141984

Yersinia pestis initiates infection by parasitism of host macrophages. In response to macrophage infections, intracellular Y. pestis can assume a filamentous cellular morphology which may mediate resistance to host cell innate immune responses. We previously observed the expression of Y. pestis tellurite resistance proteins TerD and TerE from the terZABCDE operon during macrophage infections. Others have observed a filamentous response associated with expression of tellurite resistance operon in Escherichia coli exposed to tellurite. Therefore, in this study we examine the potential role of Y. pestis tellurite resistance operon in filamentous cellular morphology during macrophage infections. In vitro treatment of Y. pestis culture with sodium tellurite (Na2TeO3) caused the bacterial cells to assume a filamentous phenotype similar to the filamentous phenotype observed during macrophage infections. A deletion mutant for genes terZAB abolished the filamentous morphologic response to tellurite exposure or intracellular parasitism, but without affecting tellurite resistance. However, a terZABCDE deletion mutant abolished both filamentous morphologic response and tellurite resistance. Complementation of the terZABCDE deletion mutant with terCDE, but not terZAB, partially restored tellurite resistance. When the terZABCDE deletion mutant was complemented with terZAB or terCDE, Y. pestis exhibited filamentous morphology during macrophage infections as well as while these complemented genes were being expressed under an in vitro condition. Further in E. coli, expression of Y. pestis terZAB, but not terCDE, conferred a filamentous phenotype. These findings support the role of Y. pestis terZAB mediation of the filamentous response phenotype; whereas, terCDE confers tellurite resistance. Although the beneficial role of filamentous morphological responses by Y. pestis during macrophage infections is yet to be fully defined, it may be a bacterial adaptive strategy to macrophage associated stresses.