中国科学院机构知识库网格
Chinese Academy of Sciences Institutional Repositories Grid
首页 机构 成果 学者
  
  1. CAS IR Grid
  2. 上海药物研究所
  3. 中国科学院上海药物研究所
Drug Degradation Caused by mce3R Mutations Confers Contezolid (MRX-I) Resistance in Mycobacterium tuberculosis

文献类型：期刊论文

作者Pi, Rui2,5; Chen, Xiaomin5; Meng, Jian4; Liu, Qingyun1,5; Chen, Yiwang5; Bei, Cheng5; Wang, Chuan5; Gao, Qian3,5
刊名ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
出版日期2022-10-18
卷号66期号:10页码:11
关键词Mycobacterium tuberculosis drug resistance contezolid Mce3R Rv1936 degradation drug resistance mechanisms
ISSN号0066-4804
DOI10.1128/aac.01034-22
通讯作者Gao, Qian(qiangao@fudan.edu.cn)
英文摘要Contezolid (MRX-I), a safer antibiotic of the oxazolidinone class, is a promising new antibiotic with potent activity against Mycobacterium tuberculosis (MTB) both in vitro and in vivo. To identify resistance mechanisms of contezolid in MTB, we isolated several in vitro spontaneous contezolid-resistant MTB mutants, which exhibited 16-fold increases in the MIC of contezolid compared with the parent strain but were still unexpectedly susceptible to linezolid. Whole-genome sequencing revealed that most of the contezolid-resistant mutants bore mutations in the mce3R gene, which encodes a transcriptional repressor. The mutations in mce3R led to markedly increased expression of a monooxygenase encoding gene Rv1936. We then characterized Rv1936 as a putative Flavin-dependent monooxygenase that catalyzes the degradation of contezolid into its inactive 2,3-dihydropyridin-4-one (DHPO) ring-opened metabolites, thereby conferring drug resistance. While contezolid is an attractive drug candidate with potent antimycobacterial activity and low toxicity, the occurrence of mutations in Mce3R should be considered when designing combination therapy using contezolid for treating tuberculosis.
WOS关键词OXAZOLIDINONE ANTIBACTERIAL AGENT ; EPOXIDE-HYDROLASE-B ; MULTIDRUG-RESISTANT ; XDR-TB ; SAFETY ; METABOLISM ; PHARMACOKINETICS ; SUSCEPTIBILITY ; TOLERABILITY ; BIOCATALYSTS
资助项目National Natural Science Foundation of China[81661128043] ; National Natural Science Foundation of China[81871625] ; [2018ZX10715-012]
WOS研究方向Microbiology ; Pharmacology & Pharmacy
语种英语
WOS记录号WOS:000863571500001
出版者AMER SOC MICROBIOLOGY
源URL[http://119.78.100.183/handle/2S10ELR8/302760]  
专题中国科学院上海药物研究所
通讯作者Gao, Qian
作者单位1.Harvard TH Chan Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA USA
2.Zhejiang Chinese Med & Western Med Integrated Hos, Hangzhou Red Cross Hosp, Cent Lab, Hangzhou, Zhejiang, Peoples R China
3.Shenzhen Third Peoples Hosp, Natl Clin Res Ctr Infect Dis, Shenzhen, Guangdong, Peoples R China
4.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai, Peoples R China
5.Fudan Univ, Sch Basic Med Sci, Shanghai Inst Infect Dis & Biosecur, Key Lab Med Mol Virol MOE NHC CAMS,Shanghai Med C, Shanghai, Peoples R China
推荐引用方式
GB/T 7714		 Pi, Rui,Chen, Xiaomin,Meng, Jian,et al. Drug Degradation Caused by mce3R Mutations Confers Contezolid (MRX-I) Resistance in Mycobacterium tuberculosis[J]. ANTIMICROBIAL AGENTS AND CHEMOTHERAPY,2022,66(10):11.
APA Pi, Rui.,Chen, Xiaomin.,Meng, Jian.,Liu, Qingyun.,Chen, Yiwang.,...&Gao, Qian.(2022).Drug Degradation Caused by mce3R Mutations Confers Contezolid (MRX-I) Resistance in Mycobacterium tuberculosis.ANTIMICROBIAL AGENTS AND CHEMOTHERAPY,66(10),11.
MLA Pi, Rui,et al."Drug Degradation Caused by mce3R Mutations Confers Contezolid (MRX-I) Resistance in Mycobacterium tuberculosis".ANTIMICROBIAL AGENTS AND CHEMOTHERAPY 66.10(2022):11.

入库方式： OAI收割

来源：上海药物研究所

浏览0
下载0
收藏0
其他版本

除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。