产生异化物耐药性的突变与高度可变的表型耐药性有关
Senamile Lale Ngema1, Navisha Dookie1, Rubeshan Perumal1,2
1Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu-Natal, Durban, South Africa.
概括
在多药耐药结核病中,高剂量异化耐药性与特定的基因突变有关. *InhA*突变意外地赋予了高水平的耐药性,而*katG*突变通常表现出中等的耐药性.
科学领域:
- 微生物学 微生物学
- 遗传学 遗传学 是一个
- 药理学 药理学是指药理学的学科.
背景情况:
- 建议使用高剂量异化治疗具有*inhA*突变的多药耐药结核病 (MDR-TB).
- 对异尼抗的基因型-表型对应的证据有限.
- 这项研究调查了与高水平异化物耐药性相关的遗传突变.
研究的目的:
- 确定与MDR-TB中高水平的表型异化物耐药性相关的遗传突变.
- 评估 *inhA* 和 *katG* 突变的基因型-表型一致性.
- 澄清临床隔离物中*inhA*和*katG*突变的耐药性概况.
主要方法:
- 52个临床MDR-TB分离物的全基因组测序.
- 使用基于MGIT的方法进行最小抑制度 (MIC) 测试.
- 对MIC分布和对突变特征的重叠指数的分析.
主要成果:
- *InhA*突变显示出意想不到的高MIC (平均33.64μg/ml) 和与*inhA* + *katG*突变 (eta=0.45) 的高重叠.
- 与预期相反, *katG* 突变主要赋予了中等级别的抗药性 (平均值为 6.79 μg/ml).
- 50%的*InhA*突变种和83.3%的*katG*突变种分别表现出高和中等耐药性.
结论:
- *InhA*突变与意外高的异化抗性水平有关.
- *katG* 突变更常与中等水平的抗药性有关,而不是高水平的抗药性.
- 这些发现挑战了关于MDR-TB治疗中基因型-表型相关性的现有假设.
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