Department of Food Science and Technology, University of Ljubljana, Ljubljana, Slovenia.
Microb Drug Resist. 2012 Oct;18(5):492-501. doi: 10.1089/mdr.2012.0017. Epub 2012 Jun 28.
The aim was to assess the potency of the efflux pump inhibitors (EPIs) phenylalanine-arginine ß-naphthylamide (PAßN) and 1-(1-naphthylmethyl)-piperazine (NMP) and the putative natural EPI phenolic (-)-epigallocatechin gallate (EGCG) for the reversal of erythromycin, ciprofloxacin, and tetracycline resistance in Campylobacter jejuni and Campylobacter coli isolates. We investigated target mutations and resistant genes involved in erythromycin and tetracycline resistance and determined the roles of the bacterial drug efflux systems (cmeB, cmeF, and cmeR) in antimicrobial resistance. Our data show that most of the high-level erythromycin resistance and all of the tetracycline resistance can be explained through mutations in 23S rRNA and the presence of the tetO gene, respectively. The EPIs show the ability to partly reverse drug resistance in these Campylobacter isolates. Based on a fourfold or greater reduction in the erythromycin minimal inhibitory concentration (MIC), PAßN and NMP had clear effects in almost of all of the isolates tested. PAßN had a highly selective action on the ciprofloxacin and tetracycline MICs. Inactivation of cmeB increased susceptibility to all of the antimicrobials tested, whereas inactivation of cmeF and cmeR had no effects. A notable decrease in resistance to erythromycin and ciprofloxacin in the presence of subinhibitory concentrations of EGCG demonstrates the resistance-modifying activities of this natural EPI, and indicates its potential use in the control of Campylobacter spp. in the food chain.
目的是评估外排泵抑制剂（EPIs）苯丙氨酸-精氨酸β-萘基酰胺（PAßN）和 1-（1-萘甲基）哌嗪（NMP）以及假定的天然外排泵抑制剂表没食子儿茶素没食子酸酯（EGCG）对弯曲杆菌属空肠亚种和弯曲杆菌属结肠亚种中红霉素、环丙沙星和四环素耐药性的逆转作用。我们研究了与红霉素和四环素耐药性相关的靶基因突变和耐药基因，并确定了细菌药物外排系统（cmeB、cmeF 和 cmeR）在抗菌药物耐药性中的作用。我们的数据表明，大多数高水平的红霉素耐药性和所有的四环素耐药性分别可以通过 23S rRNA 突变和 tetO 基因的存在来解释。EPI 显示出在这些弯曲杆菌属分离株中部分逆转药物耐药性的能力。基于红霉素最小抑菌浓度（MIC）降低四倍或以上，PAßN 和 NMP 在几乎所有测试的分离株中都具有明显的作用。PAßN 对环丙沙星和四环素 MIC 具有高度选择性作用。cmeB 的失活增加了对所有测试的抗菌药物的敏感性，而 cmeF 和 cmeR 的失活没有影响。在亚抑菌浓度 EGCG 存在下，红霉素和环丙沙星耐药性显著降低，表明该天然 EPI 具有耐药修饰活性，并表明其在控制食物链中弯曲杆菌属的潜在用途。
