Role of an RNA polymerase interacting protein, MsRbpA, from Mycobacterium smegmatis in phenotypic tolerance to rifampicin
Role of an RNA polymerase interacting protein, MsRbpA, from Mycobacterium smegmatis in phenotypic tolerance to rifampicin
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DOI：
10.1099/mic.0.033670-0
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发表时间：
2010-03-01
期刊：
影响因子：
2.8
通讯作者：
Chatterji, Dipankar
中科院分区：
文献类型：
--
作者：
Dey, Abhinav;Verma, Amit Kumar;Chatterji, Dipankar
利福平及其衍生物是目前活动性结核病标准化疗方案的前沿；它们通过抑制原核RNA聚合酶的转录活性起作用。利福平被认为与RNA聚合酶的β亚基相互作用。然而，已经观察到蛋白质与RNA聚合酶核心酶的相互作用导致其对利福平的易感性降低。随着在链霉菌中发现一种新的RNA聚合酶结合蛋白RbpA，这种机制变得更加多样化，RbpA可以减轻利福平对RNA聚合酶活性的影响。MsRbpA是耻垢分枝杆菌中RbpA的同源物。在破译MsRbpA在垢垢分枝杆菌中的作用时，我们发现它与RNA聚合酶相互作用，并在体外和体内增加利福平耐受水平。它与RNA聚合酶的β亚基相互作用。然而，在利福平存在的情况下，在相应的IC50下，发现它不能挽救利福平耐药RNA聚合酶。
Rifampicin and its derivatives are at the forefront of the current standard chemotherapeutic regimen for active tuberculosis; they act by inhibiting the transcription activity of prokaryotic RNA polymerase. Rifampicin is believed to interact with the beta subunit of RNA polymerase. However, it has been observed that protein-protein interactions with RNA polymerase core enzyme lead to its reduced susceptibility to rifampicin. This mechanism became more diversified with the discovery of RbpA, a novel RNA polymerase-binding protein, in Streptomyces coelicolor that could mitigate the effect of rifampicin on RNA polymerase activity. MsRbpA is a homologue of RbpA in Mycobacterium smegmatis. On deciphering the role of MsRbpA in M. smegmatis we found that it interacts with RNA polymerase and increases the rifampicin tolerance levels, both in vitro and in vivo. It interacts with the beta subunit of RNA polymerase. However, it was found to be incapable of rescuing rifampicin-resistant RNA polymerases in the presence of rifampicin at the respective IC50.