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

Abstract

Background 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.Principal Findings 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.ConclusionsThese 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.

Evolutionary study of Yersinia genomes deciphers emergence of human pathogenic species

“…We found P0 ancestor had gained different types of metabolic genes compared to the phylogroup-E species. It gained tellurite resistance genes ( ter ZABCD) and itaconate catabolic genes ( rip ABC), which had been shown by previous studies as adaptive strategies to survive inside macrophages282930. Besides, P0 ancestor had gained several virulence genes, including pil WVUSRQPONML (type IV pilus gene cluster which resides in Yersinia adhesion pathogenicity island), psa ABCEF (pH 6 antigen genes).…”

“…We found that the phylogroup-P species seemed to have expanded their ecological niche to macrophages, probably due to the acquisition of putative genes such as ter and rip loci, and the loss of two cellulose biosynthesis loci ( bcs ), which could also increase virulence inside the macrophages28293033. This might allow the phylogroup-P species to occupy the macrophage compared to its predecessor and phylogroup-E, which usually adapt to the intestinal tracts.…”

Klebsiella variicola and Klebsiella quasipneumoniae with capacity to adapt to clinical and plant settings

“…30 Tellurite resistance is needed to colonize macrophages. 31 The TerABCDEWXYZ proteins cluster was identified in 12.9% (4/31) and 12.5% (1/8), of K. variicola and K. quasipneumoniae, all of human origin. K. variicola 8917 isolate was described as hypermucoviscous.…”

Peer Review #1 of "Comparative genomic analysis of a new tellurite-resistant Psychrobacter strain isolated from the Antarctic Peninsula (v0.3)"

“…Thus terZABCDEF, terZABCDE and TerABD present in E. coli O157:H7, Proteus sp. and D. radiodurans, respectively, are operons (Makarova et al, 2001;Ponnusamy and Clinkenbeard, 2015;Taylor et al, 2002). The Psychrobacter genus represents an exception to this rule, with terA lying in the opposite transcriptional orientation ( Supplementary Figure 1).…”