Interaction of ArmZ with the DNA-binding domain of MexZ induces expression of mexXY multidrug efflux pump genes and antimicrobial resistance in Pseudomonas aeruginosa.

Interaction of ArmZ with the DNA-binding domain of MexZ induces expression of mexXY multidrug efflux pump genes and antimicrobial resistance in Pseudomonas aeruginosa. Antimicrob Agents Chemother. 2019 Sep 16;: Authors: Kawalek A, Modrzejewska M, Zieniuk B, Bartosik AA, Jagura-Burdzy G Abstract Multidrug efflux pumps play an important role in antibiotic resistance in bacteria. In Pseudomonas aeruginosa, MexXY pump provides intrinsic resistance to many antimicrobials, including aminoglycosides. The expression of mexXY operon is negatively regulated by MexZ repressor. The repression is alleviated in response to the antibiotic-induced ribosome stress, which results in increased synthesis of anti-repressor ArmZ, interacting with MexZ. The molecular mechanism of MexZ inactivation by ArmZ is not known. Here, we showed that the N-terminal part of MexZ, encompassing the DNA-binding domain, is required for interaction with ArmZ. Using the bacterial two hybrid system based mutant screening and pull-down analyses we identified substitutions in MexZ that diminished (R3S, K6E, R13H) or completely impaired (K53E) the interaction with ArmZ without blocking MexZ activity as a transcriptional repressor. Introduction of corresponding mexZ missense mutations into P aeruginosa PAO1161 chromosome impaired (mexZ K6E, mexZ R13H) or blocked (mexZ K53E) tetracycline mediated induction of mexY expression. Concomitantly, PAO1161 mexZ K53E strain was more susce...
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Tags: Antimicrob Agents Chemother Source Type: research