Bacteria primed by antimicrobial peptides develop tolerance and persist

PLoS Pathog. 2021 Mar 31;17(3):e1009443. doi: 10.1371/journal.ppat.1009443. eCollection 2021 Mar.

Abstract

Antimicrobial peptides (AMPs) are key components of innate immune defenses. Because of the antibiotic crisis, AMPs have also come into focus as new drugs. Here, we explore whether prior exposure to sub-lethal doses of AMPs increases bacterial survival and abets the evolution of resistance. We show that Escherichia coli primed by sub-lethal doses of AMPs develop tolerance and increase persistence by producing curli or colanic acid, responses linked to biofilm formation. We develop a population dynamic model that predicts that priming delays the clearance of infections and fuels the evolution of resistance. The effects we describe should apply to many AMPs and other drugs that target the cell surface. The optimal strategy to tackle tolerant or persistent cells requires high concentrations of AMPs and fast and long-lasting expression. Our findings also offer a new understanding of non-inherited drug resistance as an adaptive response and could lead to measures that slow the evolution of resistance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antimicrobial Cationic Peptides / pharmacology*
  • Bacterial Proteins / metabolism
  • Drug Resistance, Microbial / physiology*
  • Escherichia coli / drug effects*
  • Escherichia coli / metabolism*
  • Melitten / pharmacology
  • Polysaccharides / metabolism

Substances

  • Antimicrobial Cationic Peptides
  • Bacterial Proteins
  • Polysaccharides
  • Crl protein, Bacteria
  • Melitten
  • colanic acid
  • pexiganan

Associated data

  • Dryad/10.5061/dryad.j9kd51cbw

Grants and funding

ARR and JR were funded by DFG project SFB 973 (C5). RRR and DYB were funded by ETH Zurich (ETH-41 15-2). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.