The mexEF-oprN multidrug efflux operon of P. aeruginosa: regulation by the MexT activator in response to nitrosative stress and chloramphenicol
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Fetar, Hossam, Christie, Gilmour, Rachel, Klinoski, Daigle, Denis, Dean, Charles and Poole, Keith (2011) The mexEF-oprN multidrug efflux operon of P. aeruginosa: regulation by the MexT activator in response to nitrosative stress and chloramphenicol. Antimicrobial Agents and Chemotherapy, 55 (2). pp. 508-514. ISSN 0066-4804
Abstract
A null mutation in the mexS gene of P. aeruginosa yielded increased expression of a 3-gene operon containing a gene, xenB, whose product is highly homologous to a xenobiotic reductase in Pseudomonas fluorescens shown to remove nitro groups from trinitrotouleune and nitroglycerin (Blehert, D.S. et al. 1999. J. Bacteriol. 181:6254). This expression, which paralleled an increase in mexEF-oprN expression in the same mutant, was, like mexEF-oprN, dependent on the MexT LysR-family positive regulator previously implicated in mexEF-oprN expression. As nitrosation is a well-known product of nitrosative stress, a role of xenB (and the co-regulated mexEF-oprN) in a nitrosative stress response was hypothesized and tested. Using s-nitrosoglutathione (GSNO) as a source of nitrosative stress, expression of xenB and mexEF-oprN was shown to be GSNO-inducible, though in the case of xenB this was only seen in a mutant lacking MexEF-OprN. In both instances this GSNO-inducible expression was dependent upon MexT. The mexS gene encoding a probable oxidoreductase was also inducible by GSNO though, again, only in the absence of MexEF-OprN. Expression of the OprD outer membrane amino acid/peptide porin gene that is characteristically inversely regulated with mexEF-oprN in nfxC and mexS mutants was reduced in the presence of GSNO, though this was independent of MexT. Chloramphenicol, a nitroaromatic antimicrobial that is a substrate for MexEF-OprN was shown to induce mexEF-oprN, but not xenB or mexS, possibly because it resembles a nitrosated nitrosative stress product accommodated by MexEF-OprN. Again, this was dependent upon the MexT regulator.
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| Keywords: | MexEF-OprN Efflux nitrosative stress |
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| Date Deposited: | 13 Oct 2015 13:16 |
| Last Modified: | 13 Oct 2015 13:16 |
| URI: | https://oak.novartis.com/id/eprint/2070 |