机构：[1]The Joint Center for Infection and Immunity, Guangzhou Institute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou, China,[2]Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China,[3]Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Department of Infectious Diseases, Institute for Viral Hepatitis, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China,[4]Department of Respiratory Medicine, The First People’s Hospital of Yunnan Province, Kunming, China,内科片呼吸与危重症医学科云南省第一人民医院[5]Affiliated Hospital of Kunming University of Science and Technology, Kunming, China,[6]State Key Laboratory Breeding Base of Eco-Environment and Bio-Resource of the Three Gorges Area, Key Laboratory of Eco-Environments in Three Gorges Reservoir Region, Ministry of Education, School of Life Sciences, Institute of Modern Biopharmaceuticals, Southwest University, Chongqing, China
The increasing incidence of drug-resistant tuberculosis is still an emergency for global public health and a major obstacle to tuberculosis treatment. Therefore, deciphering the novel mechanisms of mycobacterial antibiotic resistance is crucial for combatting the rapid emergence of drug-resistant strains. In this study, we identified an unexpected role of Mycobacterium smegmatis GntR family transcriptional regulator MSMEG_5174 and its homologous gene Mycobacterium tuberculosis Rv1152 in aminoglycoside antibiotic resistance. Deficiency of MSMEG_5174 rendered Mycobacterium smegmatis highly resistant to aminoglycoside antibiotic treatment, and ectopic expression of Rv1152 in MSMEG_5174 mutants restored antibiotic-induced bacterial killing. We further demonstrated that MSMEG_5174 negatively regulates the expression of purine metabolism-related genes and the accumulation of purine metabolites. Moreover, overexpression of xanthine dehydrogenase MSMEG_0871 or xanthine treatment elicited a significant decrease in aminoglycoside antibiotic lethality for Mycobacterium smegmatis. Together, our findings revealed MSMEG_5174 as a metabolic regulator and hint toward unexplored crosstalk between purine metabolism and antibiotic resistance.
基金：
This work was supported by the National Natural Science
Foundation of China (81701979 and 31900456), the China
Postdoctoral Science Foundation (2019M650193), Guangzhou
Science and Technology Project (202102020093), Kuanren
Talents Program of The Second Affiliated Hospital of Chongqing
Medical University, and Natural Science Foundation of
Guangdong Province (2017A030313557).
第一作者机构：[1]The Joint Center for Infection and Immunity, Guangzhou Institute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou, China,[2]Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China,[3]Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Department of Infectious Diseases, Institute for Viral Hepatitis, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China,
共同第一作者：
通讯作者：
通讯机构：[1]The Joint Center for Infection and Immunity, Guangzhou Institute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou, China,[2]Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China,[3]Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Department of Infectious Diseases, Institute for Viral Hepatitis, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China,
推荐引用方式(GB/T 7714)：
Deng Wanyan,Zheng Zengzhang,Chen Yi,et al.Deficiency of GntR Family Regulator MSMEG_5174 Promotes Mycobacterium smegmatis Resistance to Aminoglycosides via Manipulating Purine Metabolism[J].FRONTIERS IN MICROBIOLOGY.2022,13:doi:10.3389/fmicb.2022.919538.
APA：
Deng, Wanyan,Zheng, Zengzhang,Chen, Yi,Yang, Maoyi,Yan, Jun...&Zeng, Huasong.(2022).Deficiency of GntR Family Regulator MSMEG_5174 Promotes Mycobacterium smegmatis Resistance to Aminoglycosides via Manipulating Purine Metabolism.FRONTIERS IN MICROBIOLOGY,13,
MLA：
Deng, Wanyan,et al."Deficiency of GntR Family Regulator MSMEG_5174 Promotes Mycobacterium smegmatis Resistance to Aminoglycosides via Manipulating Purine Metabolism".FRONTIERS IN MICROBIOLOGY 13.(2022)
生物学