Heterogeneous absorption of antimicrobial peptide LL37 in Escherichia coli cells enhances population survivability
Heterogeneous absorption of antimicrobial peptide LL37 in Escherichia coli cells enhances population survivability
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DOI：
10.7554/elife.38174
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发表时间：
2018-12-18
期刊：
影响因子：
7.7
通讯作者：
Taheri-Araghi, Sattar
中科院分区：
文献类型：
--
作者：
Snoussi, Mehdi;Talledo, John Paul;Taheri-Araghi, Sattar
抗菌肽（Antimicrobial peptides，AMP）是一种选择性靶向细菌的广谱抗生素。在这里，我们研究的活性人AMP LL37对大肠杆菌整合定量，人口和单细胞水平的实验与理论建模。我们观察到大量LL37肽被E.大肠杆菌细胞的生长受到抑制，这增加了群体的生存能力。这种转变更可能发生在细胞分裂周期的后期。具有高细胞密度的培养物表现出两种不同的亚群：吸收肽的非生长群体和由于其他人螯合AMP而存活的生长群体。基于该二元图的数学模型再现了相当令人惊讶的观察结果，包括最小抑制浓度随细胞密度的增加（即使在稀释培养物中）和由亚致死剂量的LL37肽引入的生长的广泛滞后。
Antimicrobial peptides (AMPs) are broad spectrum antibiotics that selectively target bacteria. Here we investigate the activity of human AMP LL37 against Escherichia coli by integrating quantitative, population and single-cell level experiments with theoretical modeling. We observe an unexpected, rapid absorption and retention of a large number of LL37 peptides by E. coli cells upon the inhibition of their growth, which increases population survivability. This transition occurs more likely in the late stage of cell division cycles. Cultures with high cell density exhibit two distinct subpopulations: a non-growing population that absorb peptides and a growing population that survive owing to the sequestration of the AMPs by others. A mathematical model based on this binary picture reproduces the rather surprising observations, including the increase of the minimum inhibitory concentration with cell density (even in dilute cultures) and the extensive lag in growth introduced by sub-lethal dosages of LL37 peptides.