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.
Highlights
Antimicrobial peptides—short, usually cationic molecules—are key effectors of innate immune defences of all multicellular life [1] and are important players at the host microbiota interface [2,3]
Animals and plants defend themselves with ancient molecules called antimicrobial peptides (AMPs) against pathogens
In natural situation such as on the skin, bacteria are often exposed to low concentrations of Antimicrobial peptides (AMPs) that do no kill
Summary
Antimicrobial peptides—short, usually cationic molecules—are key effectors of innate immune defences of all multicellular life [1] and are important players at the host microbiota interface [2,3]. Because of their evolutionary success and diversity, AMPs are considered as new antimicrobial drugs to alleviate the antibiotic resistance crisis [4] with more than two dozen currently under clinical trial [5]. This results from the bacteria’s overlapping stress responses to AMP exposition and acidic pH
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