Mext Functions as a Redox-responsive regulator modulating disulfide stress resistance in Pseudomonas aeruginosa
MetadataShow full item record
MexT is a global LysR transcriptional regulator known to modulate antibiotic resistance and virulence in Pseudomonas aeruginosa. In this study, a novel role for MexT in mediating intrinsic disulfide stress resistance was demonstrated, representing the first identified phenotype associated with inactivation of this regulator in wild-type cells. Disruption of mexT resulted in increased susceptibility to the disulfide stress elicitor diamide [diazenedicarboxylic acid bis(N,N,-di-methylamide)]. This compound is known to elicit a specific stress response via depletion of reduced glutathione and alteration of the cellular redox environment, implicating MexT in redox control. In support of this, MexT-regulated targets, including the MexEF-OprN multidrug efflux system, were induced by subinhibitory concentrations of diamide. A mexF insertion mutant also exhibited increased diamide susceptibility, implicating the MexEF-OprN efflux system in MexT-associated disulfide stress resistance. Purified MexT protein was observed to form an oligomeric complex in the presence of oxidized glutathione, with a calculated redox potential of −189 mV. This value far exceeds the thiol-disulfide redox potential of the bacterial cytoplasm, ensuring that MexT remains reduced under normal physiological conditions. MexT is activated by mutational disruption of the predicted quinone oxidoreductase encoded by mexS. Alterations in the cellular redox state were observed in a mexS mutant (PA14nfxC), supporting a model whereby the perception of MexS-associated redox signals by MexT leads to the induction of the MexEF-OprN efflux system, which, in turn, may mediate disulfide stress resistance via efflux of electrophilic compounds.
Showing items related by title, author, creator and subject.
CpxR Activates MexAB-OprM Efflux Pump Expression and Enhances Antibiotic Resistance in Both Laboratory and Clinical nalB-Type Isolates of Pseudomonas aeruginosaTian, Z.; Yi, X.; Cho, A.; O'Gara, Fergal; Wang, Y. (2016)Resistance-Nodulation-Division (RND) efflux pumps are responsible for multidrug resistance in Pseudomonas aeruginosa. In this study, we demonstrate that CpxR, previously identified as a regulator of the cell envelope ...
Morgan, Dale (2007)Bacterial resistance to non-antibiotic agents is being increasingly studied. Plasmid-mediated resistance to cationic agents, which are important biocides, has been described in antibiotic-resistant Staphylococcus aureus. ...
Newsholme, Philip; Cruzat, Vinicius; Keane, Kevin; Carlessi, Rodrigo; de Bittencourt, P. (2016)Oxidative stress and chronic inflammation are known to be associated with the development of metabolic diseases, including diabetes. Oxidative stress, an imbalance between oxidative and antioxidative systems of cells and ...