Metabolic mechanism of ceftazidime resistance in Vibrio alginolyticus
Metabolic mechanism of ceftazidime resistance in Vibrio alginolyticus
复制标题
溶藻弧菌头孢他啶耐药的代谢机制
DOI：
10.2147/idr.s179639
复制
发表时间：
2019-01-01
影响因子：
3.9
通讯作者：
Li, Hui
中科院分区：
文献类型：
--
作者：
Liu, Shi-Rao;Pen, Xuan-Xian;Li, Hui
背景微生物代谢干扰抗生素的疗效。然而，头孢菌素类抗生素广泛应用于临床，弧菌是人类和水产养殖动物的病原菌，但关于代谢对头孢菌素类抗生素介导的杀灭作用和弧菌的影响的研究却很少。目的研究头孢菌素耐药溶藻弧菌的代谢物组，分析细菌代谢在耐药和多重耐药中的作用。结果采用气相色谱-质谱联用技术分析了头孢他啶敏感的溶藻弧菌和头孢他啶耐药的溶藻弧菌的代谢物组。VA-RCAZ的代谢组学特征在于低效呼吸、低效丙酮酸循环（P循环）、增加的脂肪酸生物合成和降低的膜质子动力。糠醛和丙二酸（丙酮酸脱氢酶和琥珀酸脱氢酶（P循环酶）的抑制剂）分别增加了VA-RCAZ对抗生素的耐药性，而暴露于三氯生（抑制脂肪酸的生物合成）则降低了耐药性，这一事实证实了这一假设。结论这些结果有助于我们了解细菌耐药的机制，并可能导致更有效的治疗，管理或预防由耐药病原体引起的感染，包括弧菌属。
Background Microbial metabolism confounds antibiotic efficacy. However, information regarding effect of metabolism on cephalosporin antibiotics-mediated killing and Vibrio spp is largely absence, although the drugs are widely used in clinic and the bacteria are pathogens to both human and aquaculture animals. Purpose This study explores the metabolome of cephalosporin antibiotic-resistant Vibrio alginolyticus and analyzes the role of bacterial metabolism in drug and multidrug-resistance. Results The metabolomes of isogenic ceftazidime-resistant V. alginolyticus (VA-RCAZ) and ceftazidime-sensitive V. alginolyticus (VA-S) were analyzed using gas chromatography -mass spectrometry. The metabolome of VA-RCAZ is characterized by inefficient respiration, an inefficient pyruvate cycle (P cycle), increased biosynthesis of fatty acids and decreased membrane proton motive force. This hypothesis was confirmed by the fact that furfural and malonate, inhibitors of pyruvate dehydrogenase and succinate dehydrogenase (P cycle enzymes), respectively, increased resistance of VA-RCAZ to antibiotics, while exposure to triclosan, to inhibit biosynthesis of fatty acids, decreased resistance. Conclusion These results contribute to our understanding of mechanisms of bacterial antibiotic-resistance and may lead to more effective approaches to treat, manage or prevent infections caused by antibiotic-resistant pathogens including those of the Vibrio species.