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首页> 外文期刊>Antimicrobial agents and chemotherapy. >Molecular genetic analysis of nucleotide polymorphisms associated with ethambutol resistance in human isolates of Mycobacterium tuberculosis.
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Molecular genetic analysis of nucleotide polymorphisms associated with ethambutol resistance in human isolates of Mycobacterium tuberculosis.

机译：结核分枝杆菌人分离物中与乙胺丁醇抗性相关的核苷酸多态性的分子遗传学分析。

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Ethambutol (EMB) is a central component of drug regimens used worldwide for the treatment of tuberculosis. To gain insight into the molecular genetic basis of EMB resistance, approximately 2 Mb of five chromosomal regions with 12 genes in 75 epidemiologically unassociated EMB-resistant and 33 EMB-susceptible Mycobacterium tuberculosis strains isolated from human patients were sequenced. Seventy-six percent of EMB-resistant organisms had an amino acid replacement or other molecular change not found in EMB-susceptible strains. Thirty-eight (51%) EMB-resistant isolates had a resistance-associated mutation in only 1 of the 12 genes sequenced. Nineteen EMB-resistant isolates had resistance-associated nucleotide changes that conferred amino acid replacements or upstream potential regulatory region mutations in two or more genes. Most isolates (68%) with resistance-associated mutations in a single gene had nucleotide changes in embB, a gene encoding an arabinosyltransferase involved in cell wall biosynthesis. The majority of these mutations resulted in amino acid replacements at position 306 or 406 of EmbB. Resistance-associated mutations were also identified in several genes recently shown to be upregulated in response to exposure of M. tuberculosis to EMB in vitro, including genes in the iniA operon. Approximately one-fourth of the organisms studied lacked mutations inferred to participate in EMB resistance, a result indicating that one or more genes that mediate resistance to this drug remain to be discovered. Taken together, the results indicate that there are multiple molecular pathways to the EMB resistance phenotype.
机译：乙胺丁醇（EMB）是世界范围内用于治疗结核病的药物治疗方案的重要组成部分。为了深入了解EMB抗药性的分子遗传基础，对从人类患者中分离出来的75种与流行病学无关的EMB抗药性和33种EMB易感性结核分枝杆菌菌株中的12个基因的5个染色体区域进行了大约2 Mb的测序。在EMB敏感菌株中未发现76％的EMB耐药生物体具有氨基酸替代或其他分子变化。 38个（51％）EMB耐药分离株在12个测序基因中只有1个具有耐药相关突变。 19个抗EMB的分离株具有与耐药相关的核苷酸变化，这些变化使两个或多个基因发生氨基酸置换或上游潜在的调控区突变。大多数在单个基因中具有抗性相关突变的分离株（68％）在embB中有核苷酸变化，该基因编码参与细胞壁生物合成的阿拉伯糖基转移酶。这些突变中的大多数导致EmbB的306或406位氨基酸置换。在最近显示出响应于结核分枝杆菌体外暴露于EMB而被上调的几个基因中也鉴定出了与抗性相关的突变，包括iniA操纵子中的基因。大约四分之一的研究生物缺乏被推断参与EMB抗性的突变，结果表明仍有一个或多个介导对该药物抗性的基因尚待发现。两者合计，结果表明EMB耐药表型有多种分子途径。

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