Dead bacterial absorption of antimicrobial peptides underlies collective tolerance

Abstract

The collective tolerance towards antimicrobial peptides (APs) is thought to occur primarily through mechanisms associated with live bacterial cells. In contrast to the focus on live cells, we discover that the LL37 antimicrobial peptide kills a subpopulation of Escherichia coli, forming dead cells that absorb the remaining LL37 from the environment. Combining mathematical modelling with population and single-cell experiments, we show that bacteria absorb LL37 at a timing that coincides with the permeabilization of their cytoplasmic membranes. Furthermore, we show that one bacterial strain can absorb LL37 and protect another strain from killing by LL37. Finally, we demonstrate that the absorption of LL37 by dead bacteria can be reduced using a peptide adjuvant. In contrast to the known collective tolerance mechanisms, we show that the absorption of APs by dead bacteria is a dynamic process that leads to emergent population behaviour.