Heterogeneous Absorption of Antimicrobial Peptide LL37 in Escherichia coli Cells Enhances Population Survivability*

Antimicrobial peptides (AMPs) are broad-spectrum antibiotics that selectively target bacteria. Here, I present our recent investigations on 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 the population. Cultures with relatively high cell density exhibit two distinct subpopulations: a non-growing population that absorb peptides and a growing population that survives attributable to the sequestration of the AMPs by other cells. Comparatively, we screened several common antibiotics for their MIC as controls to juxtapose AMPs' effects on E. coli. A mathematical model based on this binary picture reproduces a quite surprising behavior of E. coli culture in the presence of LL37, including the increase of the MIC with cell density—even in dilute cultures—and the extended lag duration of growth introduced by sub-lethal dosages of LL37.