分析细胞包膜与抗生素的相互作用,揭示了多药耐药细菌对β-乳酸盐的脆弱性
Andrew M Hogan1, A S M Zisanur Rahman1, Anna Motnenko1
1Department of Microbiology, University of Manitoba, Winnipeg, Manitoba, Canada.
Nature communications
|August 9, 2023
概括
这项研究确定了影响Burkholderia cepacia复合体 (Bcc) 细菌抗生素耐药性的关键细胞外因素. 了解这些决定因素可以指导新的策略来对抗多药耐药性感染.
科学领域:
- 微生物学 微生物学
- 遗传学 遗传学是一种遗传学.
- 药理学 药理学是指药理学的学科.
背景情况:
- 伯克霍尔德里亚塞帕西亚复合体 (Bcc) 细菌具有具有挑战性的细胞外,阻碍了抗生素的进入,导致易受伤害的患者难以治疗的感染.
- 确定BCC抗生素耐药性的遗传基础对于开发有效的治疗策略至关重要.
研究的目的:
- 进行全基因组选,以识别Burkholderia cenocepacia中细胞外相关的基因,从而赋予抗生素耐药性或易感性.
- 阐明Bcc细胞外中抗生素敏感性和耐药性的机制.
主要方法:
- 构建一个高密度,随机条形编码的Burkholderia cenocepacia的转子突变库.
- 突变库暴露于19种针对细胞包膜的抗生素和使用BarSeq.的健身分析.
- 使用CRISPR干扰技术验证已识别的关联.
主要成果:
- 在基因和抗生素易感性之间确定了100多个功能关联.
- 发现了β-乳酸敏感性,二醇糖合成和无二烯酸代谢之间的联系.
- 塞夫塔齐迪姆/阿维巴克坦的疗效与PenB碳酶抑制有关,而阿维巴克坦显示出其他抗生素的更广泛的强化作用.
结论:
- 这项研究提供了Bcc细胞包裹中抗生素敏感性介质的全面概况.
- 研究结果为优先考虑抗生素点和优化组合疗法提供了见解,包括β-乳酸/β-乳酸酶抑制剂策略.
- 该研究还描述了在BCC感染中塞菲德罗科尔的活性.
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