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The mexEF-oprN multidrug efflux operon of P. aeruginosa: regulation by the MexT activator in response to nitrosative stress and chloramphenicol

Fetar, Hossam and Christie, Gilmour and Rachel, Klinoski and Daigle, Denis and 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.

Item Type: Article
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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

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