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  • Title: Molecular mechanisms of higher MICs of antibiotics and quaternary ammonium compounds for Escherichia coli isolated from bacteraemia.
    Author: Buffet-Bataillon S, Le Jeune A, Le Gall-David S, Bonnaure-Mallet M, Jolivet-Gougeon A.
    Journal: J Antimicrob Chemother; 2012 Dec; 67(12):2837-42. PubMed ID: 22904241.
    Abstract:
    OBJECTIVES: A previous study identified an association between high MICs of quaternary ammonium compounds (QACs) and antibiotic resistance. The current aim was to investigate the genetic background of this association. METHODS: Of 153 Escherichia coli clinical strains, seven were selected for their low or high MICs of antibiotics and/or QACs. Integron resistance gene contents were identified by sequencing after PCR amplification. The genes encoding the efflux pump AcrA/TolC and its regulatory regions marA, marO, marR, soxS and rob were sequenced. The gene expression of acrA, tolC, marA, marOR, soxS and rob was assessed by quantitative real-time PCR. MICs in the presence and absence of the efflux pump inhibitor phenyl-arginine-β-naphthylamide (PAβN) were compared. RESULTS: Of the seven strains, five were resistant to amoxicillin, amoxicillin/clavulanic acid and/or co-trimoxazole (trimethoprim/sulfamethoxazole) and/or had high MICs of ciprofloxacin and QACs. Four of the five harboured a class 1 integron (intI1). In three of these four strains, the presence of dfrA/sul1 and qacEΔ1 gene cassettes correlated with resistance to co-trimoxazole and high MICs of QACs. In all of the five strains, overexpression of tolC, marOR and soxS was always associated with higher MICs of antibiotics and/or QACs. PAβN reduced the MICs of ciprofloxacin and QACs, suggesting that extrusion of ciprofloxacin and QACs from bacteria depends on the AcrAB-TolC system. CONCLUSIONS: To our knowledge, this report is the first to describe dual involvement of the AcrAB-TolC system and class 1 integrons in clinical E. coli strains.
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