RbpA and sigma(B) association regulates polyphosphate levels to modulate mycobacterial isoniazid-tolerance
文献类型：期刊论文
| 作者 | Wang, Zhongwei1,2; Cumming, Bridgette M.3; Mao, Chunyou1,2; Zhu, Yan1,2; Lu, Pei1; Steyn, Adrie J. C.3,4; Chen, Shiyun1; Hu, Yangbo1 |
| 刊名 | MOLECULAR MICROBIOLOGY
 |
| 出版日期 | 2018-06-01 |
| 卷号 | 108期号:6页码:627-640 |
| ISSN号 | 0950-382X |
| DOI | 10.1111/mmi.13952 |
| 英文摘要 | To facilitate survival under drug stresses, a small population of Mycobacterium tuberculosis can tolerate bactericidal concentrations of drugs without genetic mutations. These drug-tolerant mycobacteria can be induced by environmental stresses and contribute to recalcitrant infections. However, mechanisms underlying the development of drug-tolerant mycobacteria remain obscure. Herein, we characterized a regulatory pathway which is important for the tolerance to isoniazid (INH) in Mycobacterium smegmatis. We found that the RNA polymerase binding protein RbpA associates with the stress response sigma factor sigma(B), to activate the transcription of ppk1,the gene encoding polyphosphate kinase. Subsequently, intracellular levels of inorganic polyphosphate increase to promote INH-tolerant mycobacteria. Interestingly, sigma(B) and ppk1 expression varied proportionately in mycobacterial populations and positively correlated with tolerance to INH in individual mycobacteria. Moreover, sigB and ppk1 transcription are both induced upon nutrient depletion, a condition that stimulates the formation of INH-tolerant mycobacteria. Over-expression of ppk1 in rbpA knockdown or sigB deleted strains successfully restored the number of INH-tolerant mycobacteria under both normal growth and nutrient starved conditions. These data suggest that RbpA and sigma(B) regulate ppk1 expression to control drug tolerance both during the logarithmic growth phase and under the nutrition starved conditions. |
| 资助项目 | Core Facility and Technical Support at the Wuhan Institute of Virology ; National Natural Science Foundation of China[31670134] ; 135 Research Project of Wuhan Institute of Virology ; Strategic Priority Research Program of the Chinese Academy of Sciences[XDPB03] ; Youth Innovation Promotion Association CAS |
| WOS研究方向 | Biochemistry & Molecular Biology ; Microbiology |
| 语种 | 英语 |
| WOS记录号 | WOS:000434978300004 |
| 出版者 | WILEY |
| 源URL | [http://202.127.146.157/handle/2RYDP1HH/5380]  |
| 专题 | 中国科学院武汉植物园 |
| 通讯作者 | Chen, Shiyun; Hu, Yangbo |
| 作者单位 | 1.Chinese Acad Sci, Wuhan Inst Virol, Ctr Emerging Infect Dis, Key Lab Special Pathogens & Biosafety, Wuhan, Hubei, Peoples R China 2.Univ Chinese Acad Sci, Beijing, Peoples R China 3.Africa Hlth Res Inst, Durban, South Africa 4.Univ Alabama Birmingham, Dept Microbiol, Birmingham, AL 35294 USA |
| 推荐引用方式 GB/T 7714 | Wang, Zhongwei,Cumming, Bridgette M.,Mao, Chunyou,et al. RbpA and sigma(B) association regulates polyphosphate levels to modulate mycobacterial isoniazid-tolerance[J]. MOLECULAR MICROBIOLOGY,2018,108(6):627-640. |
| APA | Wang, Zhongwei.,Cumming, Bridgette M..,Mao, Chunyou.,Zhu, Yan.,Lu, Pei.,...&Hu, Yangbo.(2018).RbpA and sigma(B) association regulates polyphosphate levels to modulate mycobacterial isoniazid-tolerance.MOLECULAR MICROBIOLOGY,108(6),627-640. |
| MLA | Wang, Zhongwei,et al."RbpA and sigma(B) association regulates polyphosphate levels to modulate mycobacterial isoniazid-tolerance".MOLECULAR MICROBIOLOGY 108.6(2018):627-640. |
入库方式： OAI收割
来源：武汉植物园
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