1. Coregulation of mexEF-oprN and oprD in P. aeruginosa.
Coregulation of mexEF-oprN and oprD in P. aeruginosa. The models represent the proposed mechanisms of coregulation of mexEF-oprN and oprD in P. aeruginosa. Each panel represents the chromosome of P. aeruginosa, highlighting the mexE, mexF, oprN, and oprD structural genes and the proposed genes involved in coregulation, mexT, mexS, and mvaT. (A) Basal expression of mexEF-oprN and oprD in wild-type P. aeruginosa. In wild-type P. aeruginosa, MexT is functionally inactive due to either the presence of suppressing mutations or the lack of a secondary effector molecule. As a result, expression of mexEF-oprN occurs at a low basal level, and expression of oprD occurs at a level sufficient to provide quantities of OprD in the outer membrane sufficient for normal cellular function. (B) MexT-associated coregulation of mexEF-oprN and oprD. In nfxC-type mutants, MexT becomes active through a mutation within the structural gene. The activated MexT protein positively regulates (green arrow) transcription of mexEF-oprN, leading to overexpression of the efflux operon and overproduction of the MexEF-OprN efflux pump. Simultaneously, MexT negatively regulates (red arrow) oprD at the transcriptional and posttranscriptional levels, leading to decreased production of OprD. (C) MexS-associated coregulation of mexEF-oprN and oprD. Loss of MexS, a putative oxidoreductase/dehydrogenase, has been suggested to cause a buildup of secondary metabolites which may serve as effector molecules for MexT. These effector molecules could bind to MexT, alter the conformational state of the regulatory protein, and transform MexT into an activating transcriptional regulator. As a result, MexT can positively regulate (green arrow) the expression of mexEF-oprN and negatively regulate (red arrow) the expression of oprD, similar to what is described for panel B. (D) MvaT-associated coregulation of mexEF-oprN and oprD. Loss of the global regulatory protein MvaT is also associated with the upregulation of the mexEF-oprN operon. The mechanism of MvaT-associated regulation has not been elucidated, but it functions independent of MexT and MexS. In contrast to the case for the MexT- and MexS-associated regulatory pathways, loss of MvaT causes an upregulation of both mexEF-oprN and oprD expression.
Philip D. Lister et al. Clin. Microbiol. Rev. 2009; doi: /CMR