谷胱甘肽生物合成的代谢重编程调节了德比对头孢曲松的耐药性。
Metabolic reprogramming of the glutathione biosynthesis modulates the resistance of Derby to ceftriaxone.
作者信息
Ji Jian, Wu Shang, Sheng Lina, Sun Jiadi, Ye Yongli, Zhang Yiyun, Zhang Yinzhi, Gong Yajun, Zhou Jianzhong, Sun Xiulan
机构信息
State Key Laboratory of Food Science and Technology, School of Food Science and Technology, Collaborative Innovation Center of Food Safety and Quality Control, Jiangnan University, Wuxi, Jiangsu 214122, China.
College of Food Science and Pharmacy, Xinjiang Agricultural University, No. 311 Nongda Dong Road, Ürümqi, Xinjiang Uygur Autonomous Region 830052, P.R. China.
出版信息
iScience. 2023 Jul 3;26(8):107263. doi: 10.1016/j.isci.2023.107263. eCollection 2023 Aug 18.
, a foodborne pathogen, has become a major public health concern because of its widespread drug resistance, including resistance to multiple drugs such as third-generation cephalosporin, ceftriaxone (CRO). However, the metabolic profile changes and associated mechanisms engendered by cephalosporin-resistant mutations remain uncharted. In this study, we have employed the LC-MS/MS metabolomics platform to determine the metabolic profiles of 138 strains of . Our results show that metabolic profiles correspond to specific serotypes, sources, processing stages, and antibiotic resistance patterns. Notably, we observed that Derby ( Derby) with drug resistance to CRO has a different metabolic status with changes in glutathione biosynthesis. Specifically, glutathione oxidized (GSSG) and citrulline abundances are greatly suppressed in CRO-resistant Derby. Furthermore, exogenous GSSG or citrulline, but not glutathione reduced (GSH), restored the susceptibility of multidrug-resistant Derby to CRO. This study establishes a strategy based on functional metabolomics to manage the survival of antibiotic-resistant bacteria.
作为一种食源性病原体，由于其广泛的耐药性，包括对第三代头孢菌素、头孢曲松（CRO）等多种药物的耐药性，已成为主要的公共卫生问题。然而，头孢菌素耐药突变引起的代谢谱变化及相关机制仍不清楚。在本研究中，我们采用液相色谱-串联质谱代谢组学平台来确定138株该菌的代谢谱。我们的结果表明，代谢谱与特定血清型、来源、加工阶段和抗生素耐药模式相对应。值得注意的是，我们观察到对CRO耐药的肠炎沙门氏菌（肠炎沙门氏菌）具有不同的代谢状态，谷胱甘肽生物合成发生了变化。具体而言，在对CRO耐药的肠炎沙门氏菌中，氧化型谷胱甘肽（GSSG）和瓜氨酸丰度被大大抑制。此外，外源性GSSG或瓜氨酸，但不是还原型谷胱甘肽（GSH），恢复了多重耐药肠炎沙门氏菌对CRO的敏感性。本研究建立了一种基于功能代谢组学的策略来控制耐药细菌的生存。
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