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三种类型初级代谢物对降低副溶血性弧菌耐药性作用效果的比较研究
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摘要
【目的】通过调节细胞代谢状态可重构耐药副溶血性弧菌对氨基糖苷类抗生素杀菌作用的敏感性。从而创建了一种有效杀死耐药副溶血性弧菌的新途径。【方法】通过表型实验比较了在亚致死浓度抗生素作用下,不同种类代谢物对耐药细菌存活率的作用影响。并通过RT-PCR进一步分析了氧化磷酸化偶联质子通道中相关重要基因sucC,gltA,nuoF,nuol,pfkA表达量随时间的变化。【结果】在分别添加10mM甘油,丙氨酸,葡萄糖代谢物培养6h后,细菌对低浓度抗生素的敏感性提高了64倍,101倍,1886倍。对照组经氧化磷酸化解偶联剂CCCP处理后,外源代谢物的添加失去作用。【结论】通过调节细菌细胞代谢水平可显著提高耐药弧菌对氨基糖苷类抗生素的敏感性。作用机制可能主要依赖于外源代谢物通过底物激活,促进三羧酸循环,增强质子动力势,提高抗生素的摄取。
[Objective]we found that aminoglycosides can be used in combination with specific metabolites can effectively eliminate multidrug-resistant Vibro parahemolyticus.This works establishes a strategy for eradicating bacterial resistance that is based on metabolism.[Methods]we studied the phenotypic change and compared the percentage survival of multi-drug resistance V.parahemolyticus aftertreatment with different metabolites.Then we observed the transcription level changes of sucC,gltA,nuoF,nuoLandpfkAduring different infection time.[Results]Our results showed that when grown in the presence of 16μg/mlkanamycin,V.parahemolyticus cell survival decreased 64-,89-,1886-fold in the presence of glycerol,alanine,glucose.Treatment with CCCP was found to abolish aminoglycoside potentiation by all of the carbon sources.[Conclusion]this study suggest that bacterial metabolism is closely tied to aminoglycoside antibiotic susceptibility.The mechanism underlying this approach is that exogenous metabolites promotes the TCA cycle by substrate activation,which in turn increases proton motive force and stimulates uptake of antibiotic.
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