Heterogeneous absorption of antimicrobial peptide LL37 in Escherichia coli cells enhances population survivability

Elife. 2018 Dec 18:7:e38174. doi: 10.7554/eLife.38174.

Abstract

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.

Keywords: E. coli; antimicrobial peptides; computational biology; infectious disease; inoculum effect; microbiology; minimum inhibitory concentration; peptide absorption; population dynamics; systems biology.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Anti-Infective Agents / metabolism*
  • Antimicrobial Cationic Peptides / metabolism*
  • Cathelicidins
  • Escherichia coli / drug effects*
  • Escherichia coli / growth & development*
  • Humans
  • Kinetics
  • Microbial Sensitivity Tests
  • Microbial Viability / drug effects*
  • Models, Theoretical
  • Protein Binding

Substances

  • Anti-Infective Agents
  • Antimicrobial Cationic Peptides
  • Cathelicidins