Rifampicin and rifabutin resistance in 1003 Mycobacterium tuberculosis clinical isolates
Rifampicin and rifabutin resistance in 1003 Mycobacterium tuberculosis clinical isolates
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DOI：
10.1093/jac/dkz048
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发表时间：
2019-06-01
影响因子：
5.2
通讯作者：
Murray, Megan
中科院分区：
文献类型：
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作者：
Farhat, Maha R.;Sixsmith, Jaimie;Murray, Megan
目标：耐药结核病仍然是一个公共卫生挑战。利福霉素是最有效的抗结核药物之一。已知它们靶向RNA聚合酶的RpoB亚基;然而，我们对利福霉素抗性如何遗传编码的理解仍然不完整。在这里，我们调查了rpoB的遗传多样性和两种利福霉素药物利福平和rifabbestival.Methods之间的交叉耐药性：我们进行了1003结核分枝杆菌临床分离株WGS，并确定两种利福霉素药物的MIC在7 H10琼脂使用间接比例法。我们在实验室菌株中产生rpoB突变体，并使用alamarBlue还原assay.Results测定其抗生素敏感性：在1003株分离株中，766株为利福平耐药，其中210株（27%）为利福平敏感; 102/210株分离株具有rpoB突变D435 V（大肠杆菌D516 V）。具有不一致耐药性的分离株携带D435 V突变的可能性是对两种药物均耐药的分离株的17.2倍（OR 17.2，95%CI 10.5-27.9，P值，
Objectives: Drug-resistant TB remains a public health challenge. Rifamycins are among the most potent anti-TB drugs. They are known to target the RpoB subunit of RNA polymerase; however, our understanding of how rifamycin resistance is genetically encoded remains incomplete. Here we investigated rpoB genetic diversity and cross-resistance between the two rifamycin drugs rifampicin and rifabutin.Methods: We performed WGS of 1003 Mycobacterium tuberculosis clinical isolates and determined MICs of both rifamycin agents on 7H10 agar using the indirect proportion method. We generated rpoB mutants in a laboratory strain and measured their antibiotic susceptibility using the alamarBlue reduction assay.Results: Of the 1003 isolates, 766 were rifampicin resistant and 210 (27%) of these were rifabutin susceptible; 102/210 isolates had the rpoB mutation D435V (Escherichia coli D516V). Isolates with discordant resistance were 17.2 times more likely to harbour a D435V mutation than those resistant to both agents (OR 17.2, 95% CI 10.5-27.9, P value,