Heterogeneous Absorption of Antimicrobial Peptide LL37 inEscherichia coliCells Enhances Population Survivability

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. Our data indicate an unexpected, rapid absorption and retention of a large number of LL37 by E. coli cells upon the inhibition of their growth, which increases the chance of survival for the rest of population. Cultures with high-enough 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 behaviors of E. coli cultures in the presence of LL37, 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.