D-海藻糖增强氨基糖苷类抗生素杀灭大肠杆菌的机制探究

Study on the Mechanism of D-trehalose Enhancing the Killing of Escherichia coli by Aminoglycoside Antibiotics

寻找高效的抗生素佐剂并研究其增效杀菌机制是目前应对细菌耐药问题的有效策略之一。为探究D-海藻糖(D-trehalose)增强氨基糖苷类抗生素杀灭大肠杆菌的机制,以大肠杆菌BW25113为研究对象,测定D-trehalose联合氨基糖苷类抗生素作用前后的ATP、NADH含量以及质子动力势(PMF),分析菌体内能量代谢和膜电位水平的变化,并通过抑菌圈实验检测对抗生素摄取的影响。结果提示:D-trehalose联合妥布霉素或庆大霉素双处理后,D-trehalose能够通过升高大肠杆菌PMF水平增加ATP合成,提高NADH水平,促进抗生素摄取,由此显著增强抗生素的杀菌效果。研究结果为开发D-海藻糖作为新型氨基糖苷类抗生素佐剂提供依据。

Finding the efficient antibiotic adjuvants and studying their synergistic bactericidal mechanism is one of the effective strategies to deal with the problem of bacterial resistance.In order to explore the mechanism of D-trehalose enhancing the killing effect of Escherichia coli by the aminoglycoside antibiotics,by taking Escherichia coli BW25113 as the research object,the contents of ATP,NADH and proton motive force(PMF)were measured before and after the treatment of D-trehalose combined with the aminoglycoside antibiotics.The changes of energy metabolism and membrane potential in bacteria were analyzed,and the effect on the uptake of antibiotics was detected by using the inhibition zone experiment.The results showed that:after the double treatment with D-trehalose combined with tobramycin or gentamycin,D-trehalose could increase the synthesis of ATP,increase the level of NADH,and promote the uptake of antibiotics by increasing the PMF level of Escherichia coli,thus significantly enhancing the bactericidal effect of antibiotics.The results of this study provided a basis for the development of Dtrehalose as a new-type aminoglycoside antibiotic adjuvant.