舍曲林对金黄色葡萄球菌多重耐药性的逆转作用

Reversal Effect of Sertraline on Multidrug Resistance of Staphylococcus aureus

以多重耐药金黄色葡萄球菌为研究对象,通过测定非抗生素类药物舍曲林与不同抗生素作用的最低抑菌浓度、生长速率、时间-杀菌曲线及实时荧光定量PCR定量检测耐药基因mecA和外排泵基因norA的转录水平,探讨舍曲林对金黄色葡萄球菌多重耐药性的逆转作用及逆转机制.结果显示:当舍曲林质量浓度高于1μg/mL时,对金黄色葡萄球菌有抑制作用;亚抑菌浓度(1/2MIC)的舍曲林和四环素联用时对金黄色葡萄球菌具有杀菌作用;当舍曲林和四环素、环丙沙星、克林霉素联用时对金黄色葡萄球菌具有协同或相加抑制作用,可使其对3种抗生素的敏感性提高75%以上;低质量浓度的舍曲林可显著降低外排泵基因norA和SCCmec基因盒中mecA基因的表达水平.实验结果表明,舍曲林能通过抑制norA和mecA等耐药基因的表达来调控金黄色葡萄球菌的多重耐药性,通过联合抑菌部分逆转金黄色葡萄球菌对多种抗生素的耐药性.

Multidrug-resistant Staphylococcus aureus(S.aureus)were taken as object to investigate the reversal effect of sertraline on multi-drug resistance of S.aureus and its reversal mechanism through the determination of minimum inhibitory concentration,growth rate,time-kill curves under the combination of non-antibiotics sertraline and different antibiotics,as well as transcriptional level of the drug resistance gene mecA and the efflux pump gene norA by real-time PCR.The results indicate that when the sertraline concentration is higher than 1μg/mL,the growths of S.aureus are inhibited;when sertraline(1/2 MIC)is combined with tetracycline,it has a bactericidal effect on S.aureus.Sertraline combined with tetracycline,ciprofloxacin,and clindamycin,it has synergistic or additive inhibitory effect on S.aureus,which could increase the sensitivity of three antibiotics by more than 75%.Low concentration of sertraline could significantly reduce the expression of the efflux pump gene norA and mecA gene in SCCmec gene cassettes of S.aureus.The results show that sertraline can regulate the multi-drug resistance of S.aureus by inhibiting the expression of resistance genes such as norA and mecA,and reverse the resistance of S.aureus to various antibiotics when it is combined with antibiotics.