ArticlePLoS biology2024
The evolution of antimicrobial peptide resistance in Pseudomonas aeruginosa is severely constrained by random peptide mixtures.
Article in PLoS biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed.
- Artificial intelligence catalyzes antimicrobial peptide design.Synthetic and systems biotechnology · 2027Review
- Retracing the origin and evolution of a cryptic antimicrobial peptide within mammalian lactoferrin.PLoS biology · 2026Article
- Role of antimicrobial peptide-based biomaterials in respiratory tract infections control.BMC microbiology · 2026Review
- Characterization of two exoUBMC microbiology · 2026Article
- A 2026 Update on Computational Approaches to the Discovery and Design of Antimicrobial Peptides.Antibiotics (Basel, Switzerland) · 2026Article
- From Host-Derived Pressures to the Environmental Anti-Antimicrobial Peptides Resistome: Mechanisms, Reservoirs and Implications for Therapeutic Peptide Design.Marine drugs · 2026Review
- Antimicrobial Peptides Against Antimicrobial-Resistant Bacteria: Focus on Machine Learning.Infection and drug resistance · 2026Review
- Rational Design, Computational Analysis and Antibacterial Activities of Synthesized Peptide-Based Molecules Targeting Quorum Sensing-Dependent Biofilm Formation inPharmaceuticals (Basel, Switzerland) · 2025Article
- Assessing the Mechanism of Action of Synthetic Nanoengineered Antimicrobial Polymers against the Bacterial Membrane ofBiomacromolecules · 2025Article
- Reconstructing the Antibiotic Pipeline: Natural Alternatives to Antibacterial Agents.Biomolecules · 2025Review
- Characteristics and Potential of KSL, KSL-W, and Dadapin-1 Antimicrobial Peptides for Preventing Infections of Orthopedic Prosthetic Devices: Identifying the Most Robust Candidate.International journal of molecular sciences · 2025Article
- Uncovering the genetic basis ofiScience · 2025Article
- Pulmonary Delivery of Antibiotics to the Lungs: Current State and Future Prospects.Pharmaceutics · 2025Review
- Single Disulfide Bond in Host Defense Thanatin Analog Peptides: Antimicrobial Activity, Atomic-Resolution Structures and Target Interactions.International journal of molecular sciences · 2024Article
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Authors and funding
8 authors.
Funding
Abstract
The prevalence of antibiotic-resistant pathogens has become a major threat to public health, requiring swift initiatives for discovering new strategies to control bacterial infections. Hence, antibiotic stewardship and rapid diagnostics, but also the development, and prudent use, of novel effective antimicrobial agents are paramount. Ideally, these agents should be less likely to select for resistance in pathogens than currently available conventional antimicrobials. The usage of antimicrobial peptides (AMPs), key components of the innate immune response, and combination therapies, have been proposed as strategies to diminish the emergence of resistance. Herein, we investigated whether newly developed random antimicrobial peptide mixtures (RPMs) can significantly reduce the risk of resistance evolution in vitro to that of single sequence AMPs, using the ESKAPE pathogen Pseudomonas aeruginosa (P. aeruginosa) as a model gram-negative bacterium. Infections of this pathogen are difficult to treat due the inherent resistance to many drug classes, enhanced by the capacity to form biofilms. P. aeruginosa was experimentally evolved in the presence of AMPs or RPMs, subsequentially assessing the extent of resistance evolution and cross-resistance/collateral sensitivity between treatments. Furthermore, the fitness costs of resistance on bacterial growth were studied and whole-genome sequencing used to investigate which mutations could be candidates for causing resistant phenotypes. Lastly, changes in the pharmacodynamics of the evolved bacterial strains were examined. Our findings suggest that using RPMs bears a much lower risk of resistance evolution compared to AMPs and mostly prevents cross-resistance development to other treatments, while maintaining (or even improving) drug sensitivity. This strengthens the case for using random cocktails of AMPs in favour of single AMPs, against which resistance evolved in vitro, providing an alternative to classic antibiotics worth pursuing.
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Registered trials
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