Deficiency of GntR Family Regulator MSMEG_5174 Promotes Mycobacterium smegmatis Resistance to Aminoglycosides via Manipulating Purine Metabolism

作者全名："Deng, Wanyan; Zheng, Zengzhang; Chen, Yi; Yang, Maoyi; Yan, Jun; Li, Wu; Zeng, Jie; Xie, Jianping; Gong, Sitang; Zeng, Huasong"

作者地址："[Deng, Wanyan; Zheng, Zengzhang; Li, Wu; Gong, Sitang; Zeng, Huasong] Guangzhou Inst Pediat, Joint Ctr Infect & Immun, Guangzhou Women & Childrens Med Ctr, Guangzhou, Peoples R China; [Deng, Wanyan; Zheng, Zengzhang; Li, Wu; Gong, Sitang; Zeng, Huasong] Chinese Acad Sci, Inst Pasteur Shanghai, Shanghai, Peoples R China; [Deng, Wanyan; Chen, Yi; Yang, Maoyi; Yan, Jun] Chongqing Med Univ, Inst Viral Hepatitis, Dept Infect Dis, Key Lab Mol Biol Infect Dis,Affiliated Hosp 2,Mini, Chongqing, Peoples R China; [Zeng, Jie] First Peoples Hosp Yunnan Prov, Dept Resp Med, Kunming, Peoples R China; [Zeng, Jie] Kunming Univ Sci & Technol, Affiliated Hosp, Kunming, Peoples R China; [Xie, Jianping] Southwest Univ, Inst Modern Biopharmaceut, Sch Life Sci, State Key Lab Breeding Base Ecoenvironm & Bioresou, Chongqing, Peoples R China"

通信作者："Deng, WY; Gong, ST; Zeng, HS (通讯作者)，Guangzhou Inst Pediat, Joint Ctr Infect & Immun, Guangzhou Women & Childrens Med Ctr, Guangzhou, Peoples R China.; Deng, WY; Gong, ST; Zeng, HS (通讯作者)，Chinese Acad Sci, Inst Pasteur Shanghai, Shanghai, Peoples R China.; Deng, WY (通讯作者)，Chongqing Med Univ, Inst Viral Hepatitis, Dept Infect Dis, Key Lab Mol Biol Infect Dis,Affiliated Hosp 2,Mini, Chongqing, Peoples R China."

来源：FRONTIERS IN MICROBIOLOGY

ESI学科分类：MICROBIOLOGY

WOS号：WOS:000831175300001

JCR分区：Q2

影响因子：5.2

年份：2022

卷号：13

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Mycobacterium smegmatis; GntR; MSMEG_5174; purine metabolism; aminoglycoside antibiotics resistance

摘要："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."

基金机构："National Natural Science Foundation of China [81701979, 31900456]; China Postdoctoral Science Foundation [2019M650193]; Guangzhou Science and Technology Project [202102020093]; Kuanren Talents Program of The Second Affiliated Hospital of Chongqing Medical University; Natural Science Foundation of Guangdong Province [2017A030313557]"

基金资助正文："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)."