Chemical-genetic profiling reveals limited cross-resistance between antimicrobial peptides with different modes of action.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 31844052.
- Also identified by DOI 10.1038/s41467-019-13618-z and PMC identifier 6915728.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Antimicrobial peptides (AMPs) are key effectors of the innate immune system and promising therapeutic agents. Yet, knowledge on how to design AMPs with minimal cross-resistance to human host-defense peptides remains limited. Here, we systematically assess the resistance determinants of Escherichia coli against 15 different AMPs using chemical-genetics and compare to the cross-resistance spectra of laboratory-evolved AMP-resistant strains. Although generalizations about AMP resistance are common in the literature, we find that AMPs with different physicochemical properties and cellular targets vary considerably in their resistance determinants. As a consequence, cross-resistance is prevalent only between AMPs with similar modes of action. Finally, our screen reveals several genes that shape susceptibility to membrane- and intracellular-targeting AMPs in an antagonistic manner. We anticipate that chemical-genetic approaches could inform future efforts to minimize cross-resistance between therapeutic and human host AMPs.
Medical subject headings
- Anti-Bacterial Agents
- Antimicrobial Cationic Peptides
- Drug Resistance, Bacterial
- Escherichia coli