环境中与菌相关的真菌向醇稳态,与Mycobacterium tuberculosis竞争
Neha Malhotra1,2, Sangmi Oh1, Peter Finin1
1Tuberculosis Research Section, LCIM, NIAID, NIH, Bethesda, MD USA.
bioRxiv : the preprint server for biology
|October 7, 2024
概括
从泥炭沼泽中分离出来的真菌产生化合物,通过耗尽其醇储备来杀死Mycobacterium tuberculosis. 这一发现揭示了一个潜在的新策略,通过针对与真菌环境共享的脆弱性来对抗结核病.
科学领域:
- 微生物学 微生物学
- 菌类学 菌类学是指菌类学.
- 生物化学 生物化学
背景情况:
- 结核菌 (Mycobacterium tuberculosis) (Mtb) 繁殖在形泥炭沼泽中,与真菌进行竞争.
- 菌类具有不同的代谢能力,包括产生抗菌化合物.
研究的目的:
- 识别表现出对Mtb.抗结核活性的真菌物种及其代谢物.
- 阐明由真菌诱导的Mtb抑制背后的分子机制.
主要方法:
- 与从藻沼泽中分离出来的真菌共同培养Mtb.
- 在Mtb暴露后进行全基因组测序和真菌RNA测序 (RNAseq).
- 通过RNAseq.对诱导的真菌代谢物和Mtb细胞反应进行化学分析.
主要成果:
- 五种真菌分离物在接触Mtb时产生了抗结核剂.
- 诱导化合物包括帕图林,氨酸和尼杜拉林A,后者的生物合成途径最近被确定.
- 这些醇反应化合物在Mtb中诱导了显著的醇应激,耗尽了mycothiol.
结论:
- 菌产生强烈的醇反应性菌毒素,这些菌毒素针对Mtb.中的一个关键漏洞.
- 这种在多种真菌系统中观察到的机制表明了对Mtb.的保守策略.
- 这些发现凸显了真菌天然产品作为新型抗结核剂的潜力.
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