Mext Functions as a Redox-responsive regulator modulating disulfide stress resistance in Pseudomonas aeruginosa
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 inact...
| Main Authors: | , , , , , , , |
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| Format: | Journal Article |
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American Society for Microbiology
2012
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| Online Access: | http://hdl.handle.net/20.500.11937/11695 |
| _version_ | 1848747874703114240 |
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| author | Fargier, E. Mac Aogáin, M. Mooij, M. Woods, D. Morrissey, J. Dobson, A. Adams, C. O'Gara, Fergal |
| author_facet | Fargier, E. Mac Aogáin, M. Mooij, M. Woods, D. Morrissey, J. Dobson, A. Adams, C. O'Gara, Fergal |
| author_sort | Fargier, E. |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | 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. |
| first_indexed | 2025-11-14T06:56:05Z |
| format | Journal Article |
| id | curtin-20.500.11937-11695 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T06:56:05Z |
| publishDate | 2012 |
| publisher | American Society for Microbiology |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-116952023-02-22T06:24:20Z Mext Functions as a Redox-responsive regulator modulating disulfide stress resistance in Pseudomonas aeruginosa Fargier, E. Mac Aogáin, M. Mooij, M. Woods, D. Morrissey, J. Dobson, A. Adams, C. O'Gara, Fergal 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. 2012 Journal Article http://hdl.handle.net/20.500.11937/11695 10.1128/JB.06632-11 American Society for Microbiology unknown |
| spellingShingle | Fargier, E. Mac Aogáin, M. Mooij, M. Woods, D. Morrissey, J. Dobson, A. Adams, C. O'Gara, Fergal Mext Functions as a Redox-responsive regulator modulating disulfide stress resistance in Pseudomonas aeruginosa |
| title | Mext Functions as a Redox-responsive regulator modulating disulfide stress resistance in Pseudomonas aeruginosa |
| title_full | Mext Functions as a Redox-responsive regulator modulating disulfide stress resistance in Pseudomonas aeruginosa |
| title_fullStr | Mext Functions as a Redox-responsive regulator modulating disulfide stress resistance in Pseudomonas aeruginosa |
| title_full_unstemmed | Mext Functions as a Redox-responsive regulator modulating disulfide stress resistance in Pseudomonas aeruginosa |
| title_short | Mext Functions as a Redox-responsive regulator modulating disulfide stress resistance in Pseudomonas aeruginosa |
| title_sort | mext functions as a redox-responsive regulator modulating disulfide stress resistance in pseudomonas aeruginosa |
| url | http://hdl.handle.net/20.500.11937/11695 |