结核菌菌 (Mycobacterium tuberculosis) 的基因组和表型特征,以及与其最密切相关的非结核菌菌
Camille Sous1, Wafa Frigui1, Alexandre Pawlik1
1Institut Pasteur, Université Paris Cité, Unit for Integrated Mycobacterial Pathogenomics, CNRS UMR 6047, Paris, France.
Microbiology spectrum
|May 3, 2024
概括
包括Mycobacterium decipiens在内的四种非结核性真菌菌 (NTM) 物种与Mycobacterium tuberculosis (Mtb) 具有基因组上的相似性. 这些NTM作为有价值的模型来研究Mtb的演变和开发新的抗结核药物.
科学领域:
- 基因组学和微生物学
- 传染性疾病 传染性疾病
- 药物发现 药物发现 药物发现
背景情况:
- 非结核性菌根 (NTM) 越来越多地被认为是机会性病原体.
- 了解NTM和Mycobacterium tuberculosis (Mtb) 之间的进化关系对于对抗结核病至关重要.
- 以前的比较物种如Mycobacterium kansasii和Mycobacterium marinum在研究mtb进化的过程中存在局限性.
研究的目的:
- 从基因组和表型上描述四种与Mtb.具有高度基因组相似性的NTM物种.
- 评估这些NTM作为低毒性NTM和Mtb之间潜在的"缺失环节".
- 评估它们作为抗结核药物发现模型的实用性.
主要方法:
- 基因组测序和对四种NTM物种的比较分析:Mycobacterium decipiens,Mycobacterium lacus,Mycobacterium riyadhense和Mycobacterium shinjukuense. 这四种NTM物种的基因组测序和比较分析.
- 现型表征包括最佳生长温度,药物耐药性分析 (利番素,异亚,乙胺醇,贝达奎林) 和细胞和小鼠模型中的毒性测定.
- 对ESAT-6和CFP-10抗原的espACD位点和ESX-1分泌物的分析.
主要成果:
- Mycobacterium decipiens被证实是与Mtb最接近的已知NTM物种,在32°C-35°C的温度下生长最佳.
- 药物耐药性模式各不相同:M. decipiens耐利芬素,异酸和乙醇;M. lacus和M. riyadhense耐异酸和乙醇;M. shinjukuense对所有三种一线药物都敏感.
- 这四种物种都对贝达奎林敏感. 在感染模型中,M. riyadhense表现出最高的毒性. M. decipiens 拥有 espACD 位,并分泌 ESAT-6/CFP-10 的细胞.
结论:
- 四种研究的NTM物种代表了了解Mtb演变和毒性机制的有价值模型.
- 它们在非BSL-3条件下适应培养,这使得它们适用于抗结核病药物查和研究.
- Mycobacterium riyadhense的意外毒性表明需要重新评估其生物安全水平.
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