Collective antibiotic tolerance: mechanisms, dynamics and intervention.
Collective antibiotic tolerance: mechanisms, dynamics and intervention.
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DOI：
10.1038/nchembio.1754
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发表时间：
2015-03
影响因子：
14.8
通讯作者：
You L
中科院分区：
文献类型：
--
作者：
Meredith HR;Srimani JK;Lee AJ;Lopatkin AJ;You L
考虑到开发新抗生素的时间尺度，细菌对每一种抗生素的抗药性都以惊人的速度产生。因此，迫切需要更有效地使用抗生素，延长现有抗生素的保质期，并将其副作用降至最低。这需要了解细菌药物反应的潜在机制。过去的研究集中在单个细胞在抗生素存在下的存活情况，作为基因突变或持久者。相比之下，一群细菌细胞可以集体存活下来，接受对单个细胞致命的抗生素治疗。这种耐受性可以通过不同的机制产生，包括与抗性有关的酶的产生，滴定介导的双稳态生长抑制，蜂群和种群间的相互作用。这些策略可以使抗生素治疗后的种群快速恢复，并为原本敏感的细菌获得遗传遗传耐药性提供一个时间窗口。在这里，我们强调针对集体抗生素耐受行为作为一种抗菌治疗策略的潜力。
Bacteria have developed resistance against every antibiotic at an alarming rate, considering the timescale at which new antibiotics are developed. Thus, there is a critical need to use antibiotics more effectively, extend the shelf life of existing antibiotics, and minimize their side effects. This requires understanding the mechanisms underlying bacterial drug responses. Past studies have focused on survival in the presence of antibiotics by individual cells, as genetic mutants or persisters. In contrast, a population of bacterial cells can collectively survive antibiotic treatments lethal to individual cells. This tolerance can arise by diverse mechanisms, including resistance-conferring enzyme production, titration-mediated bistable growth inhibition, swarming, and inter-population interactions. These strategies can enable rapid population recovery after antibiotic treatment, and provide a time window for otherwise susceptible bacteria to acquire inheritable genetic resistance. Here, we emphasize the potential for targeting collective antibiotic tolerance behaviors as an antibacterial treatment strategy.