MexR and NalD are pyocyanin-responsive transcriptional repressors of the efflux pump MexAB-OprM in Pseudomonas aeruginosa.

ABSTRACT: The secondary metabolite pyocyanin (PYO) significantly enhances the antibiotic resistance of Pseudomonas aeruginosa by inducing expression of the resistance-nodulation-cell division efflux systems. However, the mechanisms underlying the initial derepression and subsequent upregulation of MexAB-OprM, regulated by multiple transcriptional repressors, remain unclear. Here, we demonstrate that MexR and NalD, the transcriptional repressors of MexAB-OprM, function as PYO receptors, with dissociation constants of 5.17 and 7.03 μM, respectively. Electrophoretic mobility shift assays show that PYO binding to MexR and NalD induces their dissociation from the mexA promoter, leading to the derepression of mexAB-oprM expression. Structural simulations and mutagenesis assays identified residues F17, R21

SUBMITTER: Wu C 

PROVIDER: S-EPMC12571440 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature