Unité d'Hygiène Hospitalière, Pôle Microorganismes, CHU Pontchaillou, Rennes, France.
J Antimicrob Chemother. 2012 Dec;67(12):2837-42. doi: 10.1093/jac/dks321. Epub 2012 Aug 17.
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.
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.
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.
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.
先前的研究表明，季铵化合物（QAC）的高 MIC 与抗生素耐药性之间存在关联。本研究旨在探讨这种关联的遗传背景。
从 153 株临床分离的大肠杆菌中，选择 7 株对抗生素和/或 QAC 具有低或高 MIC 的菌株。通过 PCR 扩增后的测序鉴定整合子抗性基因的含量。对编码外排泵 AcrA/TolC 及其调控区 marA、marO、marR、soxS 和 rob 的基因进行测序。通过实时定量 PCR 评估 acrA、tolC、marA、marOR、soxS 和 rob 的基因表达。比较了在存在和不存在外排泵抑制剂苯丙氨酸-精氨酸-β-萘酰胺（PAβN）时的 MIC。
在所研究的 7 株菌中，有 5 株对阿莫西林、阿莫西林/克拉维酸和/或复方磺胺甲噁唑（甲氧苄啶/磺胺甲噁唑）具有耐药性，或对环丙沙星和 QAC 具有高 MIC。其中 4 株菌携带 1 类整合子（intI1）。在这 4 株菌中，有 3 株存在 dfrA/sul1 和 qacEΔ1 基因盒，与对复方磺胺甲噁唑的耐药性和 QAC 高 MIC 相关。在所有 5 株菌中，tolC、marOR 和 soxS 的过表达始终与抗生素和/或 QAC 的 MIC 升高相关。PAβN 降低了环丙沙星和 QAC 的 MIC，表明细菌中外排环丙沙星和 QAC 依赖于 AcrAB-TolC 系统。
据我们所知，本报告首次描述了 AcrAB-TolC 系统和 1 类整合子在临床大肠杆菌菌株中的双重参与。
