Department of Biology, California State University, Northridge, United States.
Department of Physics, California State University, Northridge, United States.
Elife. 2018 Dec 18;7:e38174. doi: 10.7554/eLife.38174.
Antimicrobial peptides (AMPs) are broad spectrum antibiotics that selectively target bacteria. Here we investigate the activity of human AMP LL37 against 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 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.
抗菌肽 (AMPs) 是一种广谱抗生素，能选择性地靶向细菌。在这里，我们通过整合定量、群体和单细胞水平的实验与理论建模，研究了人源 AMP LL37 对 的活性。我们观察到一个出乎意料的现象，即在抑制 生长的过程中，大量的 LL37 肽迅速被 细胞吸收并保留，从而提高了群体的存活率。这种转变更可能发生在细胞分裂周期的晚期。在高细胞密度的培养物中，存在两个明显不同的亚群：一个是非生长的群体，吸收肽；另一个是生长的群体，由于其他细胞对 AMP 的隔离而存活。基于这种二元图像的数学模型再现了相当令人惊讶的观察结果，包括最小抑菌浓度随细胞密度的增加（即使在稀培养物中）和亚致死剂量的 LL37 肽引入的生长广泛滞后。
