多种药物耐受性是由Mycobacterium abscessus的抗西格玛因子RshA中的功能丧失突变所赋予的
Wassihun Wedajo Aragaw1, Tewodros T Gebresilase2,3, Dereje A Negatu1,4
1Center for Discovery and Innovation, Hackensack Meridian Health, Nutley, New Jersey, USA.
Antimicrobial agents and chemotherapy
|October 29, 2024
概括
在RshA中发生的突变使Mycobacterium abscessus具有多种药物耐药性,作为高水平耐药性的潜在脚石,并导致肺部感染的治疗失败.
科学领域:
- 微生物学 微生物学
- 药物耐药性 药物耐药性 药物耐药性
- 菌根菌感染 菌根菌感染
背景情况:
- 非正规药物耐药性途径可以先于高水平耐药性突变.
- 了解中间耐药机制对于治疗Mycobacterium (Mab) 感染至关重要.
研究的目的:
- 为了研究马布的低水平耐药性机制.
- 识别导致中间耐药性表型的遗传突变.
主要方法:
- 使用moxifloxacin进行突变选择实验.
- 对RshA.的基因删除研究.
- 最低抑制度 (MIC) 的确定.
- 马布分离物的基因组测序.
主要成果:
- 在RshA中的功能丧失突变可重复地赋予了对多种抗生素的低水平耐药性.
- 删除RshA导致中等耐药性和显著的耐药性 (生存率高达1000倍).
- 里法布丁治疗废除了ΔrshA突变体中的高耐受性表型.
结论:
- RshA-SigH通路是Mab.中的多药耐药性的关键调节者.
- RshA突变代表了向正规耐药性迈出的重要一步,并且可以直接影响治疗结果.
- 通过RshA介导的耐药性可能会导致肺部Mab感染的治疗失败.
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