在Mycobacterium abscessuslevofloxacin耐药性上的效流影响
Tianlu Teng1,2, Suting Chen2, Fengmin Huo2
1Department of Respiratory and Critical Care Medicine, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Institute, Beijing, China.
Antimicrobial agents and chemotherapy
|April 4, 2024
概括
排泄抑制剂可以通过增加易感性来克服Mycobacterium腹中的勒沃素耐药性. 这项研究表明,排泄是发展耐药性的关键,提供了新的治疗策略.
科学领域:
- 微生物学 微生物学
- 抗微生物耐药性 抗微生物耐药性
- 分子生物学分子生物学
背景情况:
- 菌根疹菌表现出对许多抗生素的固有耐药性,耐药性机制尚不清楚.
- 排泄被怀疑是M. abscessus中抗生素耐药性的关键媒介.
- 在M. abscessus中出现的勒沃素 (LFX) 耐药性需要对潜在机制进行进一步的研究.
研究的目的:
- 为了研究排泄在Mycobacterium腹中抗性levofloxacin (LFX) 的作用.
- 为了评估排泄抑制剂 (EPI) 在逆转M. abscessus中LFX抵抗的疗效.
- 探索EPI,LFX易感性和排泄基因表达之间的相关性.
主要方法:
- 使用AlarmarBlue测定方法测试了M.菌株 (ATCC19977和60个临床分离物) 对单独LFX和EPI (维拉帕米尔,储,CCCP,DCC) 的药物敏感性.
- 在耐药菌株中测序 gyrA 和 gyrB 基因以确定突变.
- 使用qRT-PCR进行量化排泄基因转录.
主要成果:
- 所有测试的M. abscessus菌株都对LFX具有抗性;没有与抗性相关的gyrA/gyrB突变.
- EPI (CCCP,DCC,VP,RSP) 在83.3%至93.3%的隔离物中显著增加了LFX敏感性 (MIC减少了2至32倍).
- 在与EPI一起显示高LFX易感性降低的隔离物中观察到七个排泄基因的升高转录.
结论:
- 排泄抑制剂可以增强levofloxacin对Mycobacterium的体外抗菌活性.
- 在LFX耐药分离物中,排泄相关基因的过度表达表明排泄与LFX耐药性发展有关.
- 向排泄是一个潜在的策略,可以对抗M. abscessus感染中的勒沃素抗性.
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