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阿根廷结核分枝杆菌katG315和inhA - 15突变与耐药谱、遗传背景及聚集性的关系

Relation of Mycobacterium tuberculosis mutations at katG315 and inhA-15 with drug resistance profile, genetic background, and clustering in Argentina.

作者信息

Monteserin Johana, Paul Roxana, Latini Cecilia, Simboli Norberto, Yokobori Noemí, Delfederico Lucrecia, López Beatriz, Ritacco Viviana

机构信息

Instituto Nacional de Enfermedades Infecciosas INEI-ANLIS, Buenos Aires, Argentina.

Instituto Nacional de Enfermedades Infecciosas INEI-ANLIS, Buenos Aires, Argentina.

出版信息

Diagn Microbiol Infect Dis. 2017 Nov;89(3):197-201. doi: 10.1016/j.diagmicrobio.2017.07.010. Epub 2017 Jul 28.

DOI:10.1016/j.diagmicrobio.2017.07.010
PMID:28844342
Abstract

We analyzed 362 isoniazid-resistant clinical isolates of Mycobacterium tuberculosis obtained countrywide for the presence of mutation at katG315 and inhA-15 in relation to genotype, pattern of phenotypic resistance to other drugs, and ability to spread. We found the following mutation frequencies: katG315MUT/inhA-15wt 53.0%, katG315wt/inhA-15MUT 27.4%, katG315wt/inhA-15wt 19.3%, and katG315MUT/inhA-15MUT only 0.3%. Mutation at katG315 associated with the LAM superfamily; mutation at inhA-15 associated with the S family and the T1 Tuscany genotype; the combination katG315wt/inhA-15wt associated with the T1 Ghana genotype. Isolates harboring katG315MUT/inhA-15wt tended to accumulate resistance to other drugs and were more frequently found in cluster; isolates harboring katG315wt/inhA-15wt were more frequently found as orphan isolates. Although epidemiological and host factors could also be modulating the events observed, in Argentina, the systematic genotyping of drug resistant clinical isolates could help to predict an enhanced risk of transmission and a propensity to develop resistance to increasing numbers of drugs.

摘要

我们分析了全国范围内获得的362株结核分枝杆菌异烟肼耐药临床分离株,以检测katG315和inhA - 15的突变情况,及其与基因型、对其他药物的表型耐药模式和传播能力的关系。我们发现以下突变频率:katG315突变/inhA - 15野生型为53.0%,katG315野生型/inhA - 15突变为27.4%,katG315野生型/inhA - 15野生型为19.3%,而katG315突变/inhA - 15突变仅为0.3%。katG315突变与LAM超家族相关;inhA - 15突变与S家族和T1托斯卡纳基因型相关;katG315野生型/inhA - 15野生型组合与T1加纳基因型相关。携带katG315突变/inhA - 15野生型的分离株倾向于对其他药物积累耐药性,且更频繁地出现在聚集性病例中;携带katG315野生型/inhA - 15野生型的分离株更常为散发病例。尽管流行病学和宿主因素也可能调节所观察到的情况,但在阿根廷,对耐药临床分离株进行系统基因分型有助于预测传播风险增加以及对越来越多药物产生耐药性的倾向。

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