解读全球传播的诺诺耐药Clostridioides difficile中对美特龙醇耐药性的神秘机制
Abiola O Olaitan1,2, Chetna Dureja1, Madison A Youngblom3
1Center for Infectious and Inflammatory Diseases, Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, TX, USA.
Nature communications
|July 12, 2023
概括
耐诺的Clostridioides difficile菌株通常会由于 nimB基因的突变而表现出对甲醇的耐药性,这使得细菌能够降解抗生素. 这种双重耐药性有助于难以治疗的感染的传播.
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:
- 艰难菌感染 (CDI) 爆发与耐诺菌株有关.
- 甲尼达是CDI的关键抗生素,其临床疗效有所下降.
- 在C. difficile中,对美特罗尼达的耐药性与依赖血红素的表型有关.
研究的目的:
- 为了阐明C. difficile中对甲化醇耐药性的机制.
- 为了研究血红素依赖性耐药性表型的遗传基础.
- 为了探索诺基诺和美特龙醇耐药性之间的联系.
主要方法:
- 对耐美的C. difficile菌株进行基因分析.
- 基因沉默和删除实验以 nimB 基因为目标.
- 对NimB蛋白的酶活性测定.
- 与诺基诺耐药性相关的DNA旋转酶突变的分析.
主要成果:
- 在nimB促进体中的T-to-G突变 (PnimBG) 会导致构成性转录和对甲尼达的耐药性.
- 沉默或删除nimB消除了对甲化的耐药性.
- NimB 是一种依赖于血红素的酶,可以降解二甲.
- PnimBG突变与DNA回旋酶中的Thr82Ile置换同时发生,从而赋予诺基诺抗性.
结论:
- 这种PnimBG基因突变是导致C. difficile对美特龙醇耐药性的原因.
- NimB酶活性解释了依赖血红素的耐药性表型.
- 在流行性C.difficile菌株中,诺基诺和美特罗尼醇耐药性的同时出现是由特定的遗传突变驱动的.
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