Bacteria primed by antimicrobial peptides develop tolerance and persist
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.
Citation
Rodríguez-Rojas , A , Baeder , D Y , Johnston , P , Regoes , R R & Rolff , J 2021 , ' Bacteria primed by antimicrobial peptides develop tolerance and persist ' , PLoS Pathogens , vol. 17 , no. 3 , e1009443 . https://doi.org/10.1371/journal.ppat.1009443
Publication
PLoS Pathogens
Status
Peer reviewed
ISSN
1553-7366Type
Journal article
Description
Funding: ARR and JR were funded by DFG project SFB 973 (C5). RRR and DYB were funded by ETH Zurich (ETH-41 15-2).Collections
Items in the St Andrews Research Repository are protected by copyright, with all rights reserved, unless otherwise indicated.