Chovanová R, Mezovská J, Vaverková Š, Mikulášová M
Department of Molecular Biology, Faculty of Natural Sciences, Comenius University, Bratislava, Slovakia.
Department of Pharmacognosy, Faculty of Pharmacy, Comenius University, Bratislava, Slovakia.
Lett Appl Microbiol. 2015 Jul;61(1):58-62. doi: 10.1111/lam.12424. Epub 2015 May 1.
The inhibition of efflux pumps is an attractive and powerful response to the emergence of bacteria resistant to antibiotics. Essential oils (EOs) from Salvia fruticosa, Salvia officinalis and Salvia sclarea reduce the minimal inhibition concentration of tetracycline, decrease efflux of antibiotic and decrease the expression of tet(K) gene in tetracycline resistant clinical isolates of Staphylococcus epidermidis. In all the cases S. fruticosa was the best one. By using checkerboard and time-killing methods, we found synergistic interactions of EOs with tetracycline.
Our data from molecular and functional analyses of inhibitory effect of Salvia's essential oils, namely from S. fruticosa, on Tet(K) pump of Staphylococcus epidermidis and from modulatory studies may be the starting point for consecutive study of pharmacokinetic and pharmacodynamic parameters and their perspective use in combination therapy. Combination of antibiotic with efflux pump inhibitor would be expected to re-establish susceptibility of the bacteria to antibiotics that became no longer effective due to bacterial resistance through the efflux pumps. The inhibition of an efflux pump can potentially improve the clinical efficacy of an antibiotic and simultaneously decrease the selection of resistant mutants.
抑制外排泵是应对细菌对抗生素产生耐药性的一种有吸引力且有效的方法。来自圆叶鼠尾草、药用鼠尾草和欧鼠尾草的精油可降低四环素的最低抑菌浓度，减少抗生素外排，并降低表皮葡萄球菌四环素耐药临床分离株中tet(K)基因的表达。在所有情况下，圆叶鼠尾草的效果最佳。通过棋盘法和时间杀菌法，我们发现精油与四环素具有协同相互作用。
我们对鼠尾草精油（即圆叶鼠尾草精油）对表皮葡萄球菌Tet(K)泵的抑制作用进行分子和功能分析以及调节研究的数据，可能是后续研究药代动力学和药效学参数及其在联合治疗中的潜在应用的起点。抗生素与外排泵抑制剂联合使用有望恢复细菌对因外排泵导致耐药而失效的抗生素的敏感性。抑制外排泵可能会提高抗生素的临床疗效，同时减少耐药突变体的产生。
