优化滞后时间是进化细菌群体抗生素耐受性的基础
Ofer Fridman1, Amir Goldberg1, Irine Ronin1
1Racah Institute of Physics, The Sudarsky Center for Computational Biology and the Center for NanoScience, Edmond J. Safra Campus, The Hebrew University, Jerusalem 91904, Israel.
Nature
|July 22, 2014
概括
细菌通过调整其在再生之前的滞后时间来对抗生素产生耐受性,并优化其以匹配治疗间隔. 这种称为"耐受性延迟" (tbl) 的适应发生在耐药性发展之前,并且在高抗生素度下对细菌生存至关重要.
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:
- 抗生素耐药性和耐受性是对抗生素压力的关键细菌生存策略,但耐受性演变的理解较少.
- 耐药性允许在低抗生素度下生长,而耐受性则允许在高度下在有限的时间内存活.
研究的目的:
- 在间歇性,高度抗生素暴露下研究细菌耐受性和耐药性的演变.
- 描述与细菌适应抗生素应激相关的遗传和表型变化.
主要方法:
- 在间歇性高剂量抗生素治疗下,细菌群体的演变.
- 在人口和单细胞水平上进行表型分析,重点关注滞后时间和耐药性.
- 全基因组测序以确定对观察到的表型负责的遗传突变和基因.
主要成果:
- 进化后的细菌菌株在通过遗传突变获得耐药性之前先发展出耐受性.
- 观察到单细胞滞后时间的显著增加,优化以匹配抗生素暴露间隔.
- 确定了"耐受性延迟" (tbl) 现型,并与特定的基因联系在一起.
结论:
- 滞后时间优化是对间歇性高剂量抗生素压力的首要适应性反应,先于耐药性的演变.
- 了解"延迟耐受性"对于制定打击抗生素耐药性的策略至关重要.
- 针对滞后时间调节可以提供新的方法来提高抗生素的疗效和预防治疗失败.
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