Cyclic di-gmp regulates mycobacterium tuberculosis resistance to ethionamide
文献类型：期刊论文
| 作者 | Zhang, Hai-Nan1; Xu, Zhao-Wei1; Jiang, He-Wei1; Wu, Fan-Lin1; He, Xiang1; Liu, Yin1; Guo, Shu-Juan1; Li, Yang1; Bi, Li-Jun4,5,6,7,8; Deng, Jiao-Yu9 |
| 刊名 | Scientific reports
 |
| 出版日期 | 2017-07-19 |
| 卷号 | 7页码:12 |
| ISSN号 | 2045-2322 |
| DOI | 10.1038/s41598-017-06289-7 |
| 通讯作者 | Tao, sheng-ce(taosc@sjtu.edu.cn) |
| 英文摘要 | Tuberculosis is still on the top of infectious diseases list on both mobility and mortality, especially due to drug-resistance of mycobacterium tuberculosis (m.tb). ethionamide (eth) is one of effective second line anti-tb drugs, a synthetic compound similar to isoniazid (inh) structurally, with existing severe problem of eth resistance. eth is a prodrug, which is activated by etha inside m.tb, and etha is transcriptionally repressed by ethr. we found that c-di-gmp could bind ethr, enhanced the binding of ethr to the promoter of etha, and then repressed the transcription of etha, thus caused resistance of m.tb to eth. through docking analysis and in vitro validation, we identified that c-di-gmp binds 3 amino acids of ethr, i.e., q125, r181 and e190, while the first 2 were the major binding sites. homology analysis showed that ethr was highly conservative among mycobacteria. further docking analysis showed that c-di-gmp preferentially bound proteins of tetr family at the junction hole of symmetric dimer or tetramer proteins. our results suggest a possible drug-resistance mechanism of eth through the regulation of ethr by c-di-gmp. |
| WOS关键词 | ANTITUBERCULOSIS DRUG ETHIONAMIDE ; TRANSCRIPTIONAL REPRESSOR ETHR ; LONG-TERM SURVIVAL ; PSEUDOMONAS-AERUGINOSA ; GENE-EXPRESSION ; PROTEIN ; SMEGMATIS ; MUTATIONS ; INHA ; SUSCEPTIBILITY |
| WOS研究方向 | Science & Technology - Other Topics |
| WOS类目 | Multidisciplinary Sciences |
| 语种 | 英语 |
| WOS记录号 | WOS:000405895000012 |
| 出版者 | NATURE PUBLISHING GROUP |
| URI标识 | http://www.irgrid.ac.cn/handle/1471x/2373408 |
| 专题 | 武汉病毒研究所 |
| 通讯作者 | Tao, Sheng-Ce |
| 作者单位 | 1.Shanghai Jiao Tong Univ, Minist Educ, Key Lab Syst Biomed, Shanghai Ctr Syst Biomed, Shanghai 200240, Peoples R China 2.Shanghai Jiao Tong Univ, Sch Biomed Engn, Shanghai 200240, Peoples R China 3.Shanghai Jiao Tong Univ, State Key Lab Oncogenes & Related Genes, Shanghai 200240, Peoples R China 4.Chinese Acad Sci, Inst Biophys, Key Lab Noncoding RNA, Natl Key Lab Biomacromol, Beijing 100101, Peoples R China 5.Chinese Acad Sci, Inst Biophys, Key Lab Prot & Peptide Pharmaceut, Beijing 100101, Peoples R China 6.TB Healthcare Biotechnol Co Ltd, Foshan 528000, Guangdong, Peoples R China 7.Foshan Univ, Sch Stomatol & Med, Foshan 528000, Guangdong, Peoples R China 8.Guangdong Prov Key Lab TB Syst Biol & Translat Me, Foshan 528000, Peoples R China 9.Chinese Acad Sci, Wuhan Inst Virol, State Key Lab Virol, Wuhan 430071, Hubei, Peoples R China |
| 推荐引用方式 GB/T 7714 | Zhang, Hai-Nan,Xu, Zhao-Wei,Jiang, He-Wei,et al. Cyclic di-gmp regulates mycobacterium tuberculosis resistance to ethionamide[J]. Scientific reports,2017,7:12. |
| APA | Zhang, Hai-Nan.,Xu, Zhao-Wei.,Jiang, He-Wei.,Wu, Fan-Lin.,He, Xiang.,...&Tao, Sheng-Ce.(2017).Cyclic di-gmp regulates mycobacterium tuberculosis resistance to ethionamide.Scientific reports,7,12. |
| MLA | Zhang, Hai-Nan,et al."Cyclic di-gmp regulates mycobacterium tuberculosis resistance to ethionamide".Scientific reports 7(2017):12. |
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来源：武汉病毒研究所
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