Major facilitator superfamily MfsA contributes to multidrug resistance in emerging nosocomial pathogenStenotrophomonas maltophilia: Table 1.

Sir, Stenotrophomonas maltophilia has become one of the important pathogens causing hospital-acquired infections. Inherited resistance of this bacterium to multiple antimicrobial agents has led to both increased patient mortality rates and higher treatment costs. Genome sequence analysis shows that S. maltophilia K279a is well equipped with intrinsic mechanisms of multidrug resistance, including multidrug efflux pumps, antibiotic degradation enzymes (β-lactamases) and drug-modifying enzymes (chloramphenicol acetyltransferase, aminoglycoside phosphotransferase and aminoglycoside acetyltransferase).1 Major facilitator superfamily (MFS) proteins are membrane efflux pumps that contribute to the active transport of various substances such as toxins and xenobiotics.2 These proteins have been seen to play some role in the multidrug resistance of pathogenic bacteria in both Gram-positive and Gram-negative organisms.3,4 We have reported the contribution of MfsA (Smlt1083), an MFS efflux pump, which belongs to a subfamily of the substrate:H+ antiporter with 14 transmembrane domains (DHA14), to paraquat resistance of S. maltophilia. Its expression is inducible and controlled by SoxR, a superoxide/redox cycling drug sensor and transcriptional regulator.5 In this letter, the role of mfsA in antimicrobial resistance was assessed in the WT K279a, a ΔmfsA mutant constructed from S. maltophilia K279a, using gene deletion, and a ΔmfsA mutant complemented strain (ΔmfsA::mfsA) carrying mfsA, transposed, using a mini-Tn7 transposon.5 The MICs of diverse classes of antibiotics for the ΔmfsA mutant were determined. The ΔmfsA mutant showed increased susceptibility to different classes of antibiotics such as aminoglycosides (kanamycin, streptomycin and neomycin), cephalosporins (cefazolin and cefalexin), the macrolide erythromycin, fluoroquinolones (ciprofloxacin, norfloxacin, levofloxacin and ofloxacin), rifampicin, tetracycline and chloramphenicol (Table 1). No change was observed in susceptibility to quaternary ammonium compounds (QACs), except for paraquat (Table 1). The results indicated that MfsA contributes to resistance to multiple, structurally unrelated antibiotics in S. maltophilia. Members of the DHA14 subfamily of MFS efflux pumps, e.g. Salmonella enterica serovar Typhimurium SmvA, are required for resistance to QACs such as paraquat, ethidium bromide, acriflavine and pyronin B.6 Deletion of amvA, an smvA homologue, in Acinetobacter baumannii increased susceptibility to several QACs and to antibiotics such as erythromycin, ciprofloxacin and novobiocin.4 The patterns of drug resistance mediated by members of DHA14 appear to vary among different bacterial species.