The reciprocal regulations of Omp36 and Omp35 (OmpF and OmpC-like, respectively) have been established in E. aerogenes as well [15]. Tight regulation of porin expression is crucial for bacterial adaptation to environments, which is mediated by a two-component system EnvZ/OmpR [2, 16, 17]. Likewise, four (tandem F1-F2-F3, and F4) and three (tandem C1-C2-C3) OmpR consensus-like sequences have been determined in the DNA regions upstream of ompF and ompC in E. coli, respectively. At low osmolarity,

OmpR-P binds cooperatively to F1-F2 or F1-F2-F3 in order to activate the transcription of ompF; meanwhile, it only occupies C1, which is not sufficient to activate the transcription of ompC. At high osmolarity, C2-C3 becomes occupied by OmpR-P with the elevated cellular OmpR-P levels, resulting in the ompC expression. Moreover, OmpR-P also MK-1775 binds to F4, which is a weak OmpR-P-binding site located 260 bp upstream of F1-F2-F3 to form a loop. In turn,

this interferes with the binding of OmpR-P to F1-F2-F3, so as to block the ompF transcription. As a member of the Enterobacteriaceae family, the genus Yersinia includes three human-pathogenic species, namely, Y. pestis, Y. pseudotuberculosis, and Y. enterocolitica. Y. pestis causes the deadly plague, while the latter two only cause non-fatal gastroenteric diseases [18]. Y. pestis LY2874455 in vitro has evolved recently (from the evolutionary point of view) from Y. pseudotuberculosis by a process combining Lonafarnib gene acquisition, loss and inactivation, while Y. enterocolitica represents a far distinct evolutionary lineage [18]. Yersinia ompF, C, and X contains conservative amino acid residues or domains typical among porins [7, 19–21]. However, regulation of porins in Y. pestis is not yet fully understood. Data presented here disclose that OmpR is involved in the survival of Y. pestis within macrophages and in building resistance against various environmental perturbations including osmotic stress. DNA microarray and quantitative RT-PCR have been employed to identify a set of OmpR-dependent genes in Y. pestis. Y. pestis OmpR STA-9090 mouse simulates ompC, F, X, and R directly by occupying the target promoter regions. Noticeably,

there is an inducible expression of all of ompF, C, X, and R at high osmolarity in Y. pestis, in contrast to the reciprocal regulation of OmpF and OmpC in E. coli. The main difference is that ompF expression is not repressed at high osmolarity in Y. pestis, which is likely due to the absence of a promoter-distal OmpR-binding site for ompF. Methods Bacterial strains The wild-type (WT) Y. pestis biovar microtus strain 201 is avirulent to humans but highly lethal to mice [22]. The 43 to 666 base pairs of ompR (720bp in total length) were replaced by the kanamycin resistance cassette using the one-step inactivation method based on the lambda Red phage recombination system, with the helper plasmid pKD46, to generate the ompR mutants of Y.