论文标题
营养限制引起的抗生素耐受性和持久性的单细胞研究的微流体研究
Microfluidics for single-cell study of antibiotic tolerance and persistence induced by nutrient limitation
论文作者
论文摘要
营养限制是抗生素耐受性和持久性的最常见触发因素之一。在这里，我们提出了两个微流体设置，以研究养分可用性的空间和时间变化如何导致细菌对抗生素的存活增加。第一个设置旨在模仿空间结构化种群中细菌的生长动力学（例如生物膜），可用于研究养分可利用性的空间梯度如何由人群的集体代谢活性，增加抗生素耐受性所产生。第二个设置捕获了细菌在自然界中经常遇到的盛宴和罕见周期的动力学，可用于研究饥饿后表型异质性在生长恢复中如何增加克隆细菌种群的存活。在这两种设置中，都可以在单细胞水平上测量细菌的生长速率和代谢活性。这对于建立对养分可用性的时空变化的机械理解很有用，可以触发细菌进入表型状态，从而增加其对抗生素的耐受性。
Nutrient limitation is one of the most common triggers of antibiotic tolerance and persistence. Here, we present two microfluidic setups to study how spatial and temporal variation in nutrient availability lead to increased survival of bacteria to antibiotics. The first setup is designed to mimic the growth dynamics of bacteria in spatially structured populations (e.g. biofilms) and can be used to study how spatial gradients in nutrient availability, created by the collective metabolic activity of a population, increase antibiotic tolerance. The second setup captures the dynamics of feast-and-famine cycles that bacteria recurrently encounter in nature, and can be used to study how phenotypic heterogeneity in growth resumption after starvation increases survival of clonal bacterial populations. In both setups, the growth rates and metabolic activity of bacteria can be measured at the single-cell level. This is useful to build a mechanistic understanding of how spatiotemporal variation in nutrient availability triggers bacteria to enter phenotypic states that increase their tolerance to antibiotics.
