菌根结核菌耐皮拉津胺胺的表型和基因型特征 - 印度,2018-2020年
Sembulingam Tamilzhalagan1, Evanslin Santus Justin1, Ashok Selvaraj1
1National Institute for Research in Tuberculosis, Indian Council of Medical Research, Chennai, India.
Frontiers in microbiology
|January 23, 2025
概括
在Mycobacterium结核病中,皮拉津胺耐药性正在增加,特别是在多药耐药结核病中. 印度全国全基因组测序发现了许多突变,主要是pncA基因,这对于预测耐药性至关重要.
科学领域:
- 微生物学 微生物学
- 遗传学 是一个遗传学.
- 公共卫生 公共卫生
背景情况:
- 皮拉津胺 (PZA) 是结核病 (TB) 治疗的关键一线药物,有效对抗持久的结核菌 (TB) 细菌.
- 越来越多的PZA耐药性,特别是在多抗药性结核病 (MDR) 病例中,对全球结核病控制工作构成了重大挑战.
- 了解PZA耐药性的遗传基础和患病率对于有效的治疗策略至关重要.
研究的目的:
- 调查来自印度的M.结核病分离物中与PZA耐药性相关的突变的流行率和多样性.
- 探索PZA耐药性与特定的M.结核病血统和共同耐药性模式的关联.
- 评估测序pncA和panD基因的诊断准确性,以预测PZA耐药性.
主要方法:
- 整个基因组测序 (WGS) 在印度全国范围内收集的2,207M结核病分离物上进行.
- 进行了表型药物敏感性测试,以识别PZA耐药分离物.
- 世卫组织认可的分级规则被应用到新型和已知的PZA耐药性转移突变的目录.
主要成果:
- 大多数PZA耐药分离物 (77%) 在pncA基因中存在突变 (171个不同的突变被确定).
- 发现了赋予PZA耐药性的新突变,以及143个额外的pncA突变.
- 抗PZA耐药性主要与血统2相关,鉴定了8种血统特异性耐药性标记.
- 在pncA的突变解释了94%的PZA耐药性,强调其作为主要驱动因素的作用.
结论:
- 建议对整个pncA基因及其促进体进行测序,以全面预测PZA耐药性的基因型.
- 这项研究提供了关于印度PZA耐药性的重要见解,印度是结核病负担很高的国家.
- 研究结果可以通过指导诊断方法和治疗方案,为结核病预防和控制策略提供信息和增强.
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