Metabolic reprogramming of the glutathione biosynthesis modulates the resistance of Salmonella Derby to ceftriaxone
Jian Ji,
Shang Wu,
Lina Sheng,
Jiadi Sun,
Yongli Ye,
Yiyun Zhang,
Yinzhi Zhang,
Yajun Gong,
Jianzhong Zhou,
Xiulan Sun
Affiliations
Jian Ji
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
Shang Wu
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
Lina Sheng
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
Jiadi Sun
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
Yongli Ye
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
Yiyun Zhang
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
Yinzhi Zhang
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
Yajun Gong
College of Food Science and Pharmacy, Xinjiang Agricultural University, No. 311 Nongda Dong Road, Ürümqi, Xinjiang Uygur Autonomous Region 830052, P.R. China
Jianzhong Zhou
College of Food Science and Pharmacy, Xinjiang Agricultural University, No. 311 Nongda Dong Road, Ürümqi, Xinjiang Uygur Autonomous Region 830052, P.R. China
Xiulan Sun
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; Yixing Institute of Food and Biotechnology, No. 19, Wenzhuang Road, Qiting Street, Yixing City, Wuxi 214200, China; Corresponding author
Summary: Salmonella, 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 Salmonella. Our results show that metabolic profiles correspond to specific serotypes, sources, processing stages, and antibiotic resistance patterns. Notably, we observed that Salmonella Derby (S. 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 S. Derby. Furthermore, exogenous GSSG or citrulline, but not glutathione reduced (GSH), restored the susceptibility of multidrug-resistant S. Derby to CRO. This study establishes a strategy based on functional metabolomics to manage the survival of antibiotic-resistant bacteria.
