Srivastava Shashikant, Ayyagari Archana, Dhole Tapan N, Nyati Kishan K, Dwivedi Shiv K
Department of Microbiology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014, India.
Int J Med Microbiol. 2009 Apr;299(4):269-80. doi: 10.1016/j.ijmm.2008.07.001. Epub 2008 Nov 17.
The emb locus has been considered a target for ethambutol (EMB). Substitutions of codon 306 in Mycobacterium tuberculosis embB have been shown to be the most frequent and predictive mutations for EMB resistance; however, recent reports question the biological role of this mutation. We sequenced embB, embC and embR of 44 EMB-resistant M. tuberculosis strains and found that 30/44 (68.1%) strains had a resistance-associated mutation in one of the three genes sequenced. The majority of these mutations resulted in amino acid replacements at codon 306, 368, 378, and 406 of EmbB. The most common mutation reported in EmbC was at codon 270, followed by mutation at codon 297. Novel mutations were also reported in EmbR. Mutations in embC and embR were usually present together with mutations in embB. We found 41/44 EMB-resistant isolates to be resistant to other antituberculosis drugs as well. Our data confirm that mutation at emb306 does not confer resistance to EMB but is a rather common polymorphism in clinical strains of M. tuberculosis predisposing them to the development of any type of drug resistance.
emb基因座被认为是乙胺丁醇（EMB）的作用靶点。结核分枝杆菌embB基因中密码子306的替换已被证明是EMB耐药最常见且具有预测性的突变；然而，最近的报告对这种突变的生物学作用提出了质疑。我们对44株耐EMB的结核分枝杆菌菌株的embB、embC和embR进行了测序，发现44株中有30株（68.1%）在测序的三个基因之一中存在与耐药相关的突变。这些突变大多数导致EmbB的密码子306、368、378和406处的氨基酸替换。EmbC中报告最常见的突变位于密码子270，其次是密码子297处的突变。EmbR中也报告了新的突变。embC和embR中的突变通常与embB中的突变同时存在。我们发现44株耐EMB分离株中有41株也对其他抗结核药物耐药。我们的数据证实，emb306处的突变并不赋予对EMB的耐药性，而是结核分枝杆菌临床菌株中一种相当常见的多态性，使它们易于产生任何类型的耐药性。
