Figure

1 Comparison of porin regulation by OmpR and CRP in E. coli and Y. pestis. The OmpR-mediated reciprocal regulation of OmpF and OmpC Selleck Tipifarnib in E. coli was discussed in the text [2, 7, 8]. In addition, CRP controlled the production of porins indirectly through its direct regulation of OmpR/EnvZ in E. coli [8, 15]. As shown in this study, Y. pestis employs a distinct mechanism indicating that CRP has no regulatory effect on the ompR-envZ operon, although it stimulates ompC and ompF directly, while repressing ompX at the same time. It is likely that OmpR and CRP respectively sense different signals, medium osmolarity, and cellular cAMP levels to regulate porin genes independently. As shown previously [12], Y. pestis

OmpR simulates ompC, F, X, and R directly by occupying the target promoter regions. Notably, all of ompF, C, X, and R give a persistent and dramatic up-regulation with the increasing medium osmolarity in Y. pestis, which is dependent of OmpR. Upon the shifting of medium osmolarity, porin expression in Y. pestis is contrary to the reciprocal regulation of OmpF and OmpC in E. coli. The F1-F2-F3 and C1-C2-C3 sites are detected for ompF and ompC of Y. pestis, respectively. Remarkably, the F4 site is absent from the upstream region of ompF, which probably destroys the OmpR-mediated blocking mechanism of ompF at high osmolarity. In E. coli, CRP acts as both repressor and activator for its own gene [28, 29]. However, no transcriptional regulatory association between CRP and its own gene was detected in Y. pestis. OmpR contributes to the building of 17-AAG clinical trial resistance against phagocytosis and survival within macrophages, which DNA Damage inhibitor is likely conserved in all the pathogenic yersiniae, namely, Y. enterocolitica [9, 10], Y. pseudotuberculosis selleck [11], and Y. pestis [12]. However, in contrast to Y. enterocolitica and Y. pseudotuberculosis, the virulence of Y. pestis is likely unaffected by the ompR null mutation. Y. pestis OmpR directly regulates ompC, F, X, and R through OmpR-promoter DNA association

(Figure 1). High osmolarity induces the transcription of all the porin genes (ompF, C, and X) in Y. pestis, in contrast with their reciprocal regulation in E. coli. The major difference is that ompF transcription 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. cAMP Receptor Protein (CRP) is a global regulator, which controls a large array of target genes [13, 14]. CRP binds to its sole cofactor cAMP to form the CRP-cAMP complex for binding to specific DNA sequence within the target promoters [13]. CRP-cAMP activates transcription by binding to specific sites, often upstream of the core promoter (-10 and -35 elements), where it directly interacts with RNA polymerase; it also represses the expression of a few genes where the binding site overlaps with or downstream the core promoter.