ArticleEvolution, medicine, and public health2022
Evolved resistance to a novel cationic peptide antibiotic requires high mutation supply.
Article in Evolution, medicine, and public health, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed.
- Non-specific Protein and Peptide Antibacterial Factors of Mammals.The protein journal · 2026Review
- Uncovering the genetic basis ofiScience · 2025Article
- History shapes regulatory and evolutionary responses to tigecycline in two reference strains ofMicrobiology (Reading, England) · 2025Article
- History shapes regulatory and evolutionary responses to tigecycline in strains ofbioRxiv : the preprint server for biology · 2025Article
- Article
- In Vitro Resistance-Predicting Studies and In Vitro Resistance-Related Parameters-A Hit-to-Lead Perspective.Pharmaceuticals (Basel, Switzerland) · 2024Review
- The evolution of antimicrobial peptide resistance in Pseudomonas aeruginosa is severely constrained by random peptide mixtures.PLoS biology · 2024Article
- Biofilm antimicrobial susceptibility through an experimental evolutionary lens.NPJ biofilms and microbiomes · 2022Review
- The Remarkable Innate Resistance of Burkholderia bacteria to Cationic Antimicrobial Peptides: Insights into the Mechanism of AMP Resistance.The Journal of membrane biology · 2022Article
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Authors and funding
7 authors.
Funding
Abstract
Background and Objectives: A key strategy for resolving the antibiotic resistance crisis is the development of new drugs with antimicrobial properties. The engineered cationic antimicrobial peptide WLBU2 (also known as PLG0206) is a promising broad-spectrum antimicrobial compound that has completed Phase I clinical studies. It has activity against Gram-negative and Gram-positive bacteria including infections associated with biofilm. No definitive mechanisms of resistance to WLBU2 have been identified. Methodology: Here, we used experimental evolution under different levels of mutation supply and whole genome sequencing (WGS) to detect the genetic pathways and probable mechanisms of resistance to this peptide. We propagated populations of wild-type and hypermutator Results: Populations that survived WLBU2 treatment acquired a minimum of two mutations, making the acquisition of resistance more difficult than for most antibiotics, which can be tolerated by mutation of a single target. Major targets of resistance to WLBU2 included the Conclusions and implications: The results show how experimental evolution and WGS can identify genetic targets and actions of new antimicrobial compounds and predict pathways to resistance of new antibiotics in clinical practice.
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