突变可以推动对抗生素多重耐药性的演变
Danna R Gifford1,2, Ernesto Berríos-Caro3,4,5, Christine Joerres1
1Division of Evolution, Infection and Genomics, School of Biological Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, United Kingdom.
PLoS genetics
|June 13, 2023
概括
具有DNA修复缺陷 (突变) 的细菌群很容易发展出多药性耐药性,甚至对联合抗生素疗法. 这挑战了当突变物存在时组合治疗的有效性,可能加速未来的耐药性演变.
科学领域:
- 微生物学 微生物学
- 进化生物学 进化生物学
- 遗传学 是一个遗传学.
背景情况:
- 抗生素耐药性是全球主要的健康威胁.
- 组合抗生素治疗是一种打击抗药性演变的策略.
- 在单个细菌基因组内出现多个耐药性突变是一个关键问题.
研究的目的:
- 研究具有DNA修复缺陷 (突变) 的细菌群体中抗生素耐药性的演变.
- 为了确定突变者是否会影响组合抗生素治疗的疗效.
- 了解不同抗生素治疗条件下的多药耐药性演变的遗传基础.
主要方法:
- 在单药和组合抗生素治疗下,大肠杆菌菌种群的实验演变.
- 全基因组测序以确定获得的突变.
- 数学建模和模拟用于分析突变率和选择动态.
主要成果:
- 细菌突变者迅速发展出对联合抗生素治疗的多药性耐药性,与野生型种群不同.
- 在药物标,排泄和DNA修复/复制基因中发现了赋予耐药性的突变.
- 突变者甚至在单一药物治疗下也促进了多抗性进化,通过与最初的抗性突变一起旅行.
- 由突变体驱动的突变率增加足以允许多抗性进化.
结论:
- 突变菌株可以显著削弱抗生素组合疗法的有效性.
- 突变的存在可能会加速对当前和未来抗生素治疗的耐药性演变.
- 了解突变者的作用对于开发针对抗生素耐药性的可持续策略至关重要.
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