JAC Advance Access originally published online on April 5, 2006
Journal of Antimicrobial Chemotherapy 2006 57(6):1070-1076; doi:10.1093/jac/dkl106
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SmeDEF-mediated antimicrobial drug resistance in Stenotrophomonas maltophilia clinical isolates having defined phylogenetic relationships
Bristol Centre for Antimicrobial Research and Evaluation, Department of Cellular and Molecular Medicine, University of Bristol, School of Medical Sciences, University Walk Bristol BS8 1TD, UK
Received 7 February 2006; returned 6 March 2006; revised 7 March 2006; accepted 7 March 2006
*Corresponding author. Tel: +44-117-9287528; Fax: +44-117-9287896; E-mail: Matthewb.Avison{at}bris.ac.uk
Objectives: To test whether smeDEF overexpression leads to a predictable multi-drug resistance phenotype in Stenotrophomonas maltophilia and to measure the frequency with which smeDEF overexpression occurs in clinical isolates and in spontaneous drug-resistant mutants.
Methods: Overexpression of smeDEF was induced in clinical isolates by the introduction of chromosomal mutations in smeT using a gene-replacement approach. Spontaneous drug-resistant mutants were selected using greater than MIC concentrations of various antimicrobial agents. Levels of smeE and smeF mRNAs were quantified using RT–PCR; MICs were determined using Etest.
Results: Of 20 spontaneous S. maltophilia drug-resistant mutants tested, four overexpressed smeDEF, but only two carried mutations within smeT. Of 30 clinical isolates tested, 6 significantly overexpressed smeDEF. One of these had an IS1246-like element embedded within the putative SmeT binding site in the smeDEF promoter. All smeDEF overexpressing derivatives of an isolate had the same resistance profile; derivatives that did not overexpress smeDEF did not share this resistance profile. However, no consistent phenotype could be associated with smeDEF overexpression in S. maltophilia isolates per se.
Conclusions: SmeT is not the only gene product that affects smeDEF expression. IS element insertion is a viable mechanism by which smeDEF expression can be derepressed. There is evidence for a background-specific, predictable effect on resistance profile when smeDEF is overexpressed, but the variability of backgrounds encountered means no general SmeDEF-mediated phenotype can be defined. There is strong evidence for the existence of as yet unidentified multi-drug efflux pumps in this species.
Keywords: efflux pumps , SmeT , nosocomial infections
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