Constitutive Activation of MexT by Amino Acid Substitutions Results in MexEF-OprN Overproduction in Clinical Isolates of Pseudomonas aeruginosa

When overproduced, the multidrug efflux system MexEF-OprN increases the resistance of Pseudomonas aeruginosa to fluoroquinolones, chloramphenicol, and trimethoprim. In this work, we demonstrate that gain-of-function mutations in the regulatory gene mexT result in oligomerization of the LysR regulator MexT, constitutive upregulation of the efflux pump, and increased resistance in clinical isolates.