SmeDEF-mediated antimicrobial drug resistance in Stenotrophomonas maltophilia clinical isolates having defined phylogenetic relationships.

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.