三醇催化转移是Mycobacterium结核病的内在因素,增强了表型异质性和多药耐药性
Hyungjin Eoh1, Jae Jin Lee1, Daniel Swanson2
1University of Southern California.
Research square
|September 24, 2024
概括
结核菌菌持续形成,对于耐药性至关重要,是由三糖代谢驱动的. 针对这种途径可以减少持久性和多药耐药结核病 (MDR-TB) 的发生率.
科学领域:
- 微生物学 微生物学
- 分子生物学分子生物学
- 药物发现 药物发现 药物发现
背景情况:
- 细菌病原体中的耐药性 (DR) 通常涉及耐药性持久细胞.
- 在Mycobacterium tuberculosis (Mtb) 中持续形成的作用及其与耐药性的联系仍然不清楚.
- 甲糖代谢的变化与Mtb持续发展和DR-TB菌株有关.
研究的目的:
- 调查三糖代谢在Mtb持续形成和药物耐药性的出现中的作用.
- 确定向三糖代谢是否可以减少持续形成和多药耐药结核病 (MDR-TB).
主要方法:
- 使用了缺乏三醇催化转移的Mtb突变.
- 在野生型和突变菌株之间比较DR突变的出现频率.
- 评估了基因和药理上的无活化对三糖催化转移对持续性结核病形成和MDR-TB发病率的影响.
主要成果:
- 具有受损三糖催化转移的Mtb突变因较低的持久形成而显著减少了DR突变的出现.
- 醇的催化转移通过增加代谢异质性和药物耐受性,提高了抗生素下Mtb的存活率.
- 耐利芬辛的Mtb表现出对其他抗生素的交叉耐药性,这与高醇催化转移活性有关,解释了MDR的发展.
- 在HN878 W-北京菌株中,三糖催化转移的非激活减少了持久性结核病的形成和MDR-TB的发病率.
结论:
- 三醇催化转移是一种内在的Mtb因子,驱动着持续性结核病的形成,交叉耐药性和MDR-TB的出现.
- 准三糖催化转移为对抗MDR-TB提供了一个潜在的治疗策略.
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