ArticleAntimicrobial agents and chemotherapy2016
Differential In Vitro and In Vivo Toxicities of Antimicrobial Peptide Prodrugs for Potential Use in Cystic Fibrosis.
Article in Antimicrobial agents and chemotherapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 31 citations in OpenAlex.
- Potent antimicrobial activity of hydrogel loaded with the antimicrobial peptide, D-Bac8cFrontiers in microbiology · 2025Article
- New Antimicrobial Strategies to Treat Multi-Drug Resistant Infections Caused by Gram-Negatives in Cystic Fibrosis.Antibiotics (Basel, Switzerland) · 2024Review
- The pharmacokinetic-pharmacodynamic modelling framework as a tool to predict drug resistance evolution.Microbiology (Reading, England) · 2023Article
- Anti-Virulence Potential of a Chionodracine-Derived Peptide against Multidrug-ResistantInternational journal of molecular sciences · 2022Article
- Acyldepsipeptide Analogues: A Future Generation Antibiotics for Tuberculosis Treatment.Pharmaceutics · 2022Review
- Elastase-Activated Antimicrobial Peptide for a Safer Pulmonary Treatment of Cystic Fibrosis Infections.Antibiotics (Basel, Switzerland) · 2022Article
- Modified poly(L-lysine)-based structures as novel antimicrobials for diabetic foot infections, anHRB open research · 2022Article
- PEGylated Oligothioetheramide Prodrugs Activated by Host Serum Proteases.Chembiochem : a European journal of chemical biology · 2021Article
- Synergies with and Resistance to Membrane-Active Peptides.Antibiotics (Basel, Switzerland) · 2020Review
- Design of N-Terminal Derivatives from a Novel Dermaseptin Exhibiting Broad-Spectrum Antimicrobial Activity against Isolates from Cystic Fibrosis Patients.Biomolecules · 2019Article
- Vibrating Mesh Nebulisation of Pro-Antimicrobial Peptides for Use in Cystic Fibrosis.Pharmaceutics · 2019Article
- Substitution of lysine for isoleucine at the center of the nonpolar face of the antimicrobial peptide, piscidin-1, leads to an increase in the rapidity of bactericidal activity and a reduction in toxicity.Infection and drug resistance · 2019Article
- The Antimicrobial Peptide lin-SB056-1 and Its Dendrimeric Derivative PreventFrontiers in microbiology · 2019Article
- Antibacterial and Potentiation Properties of Charge-Optimized Polyrotaxanes for Combating Opportunistic Bacteria.Journal of materials chemistry. B · 2018Article
- Host defense antimicrobial peptides as antibiotics: design and application strategies.Current opinion in chemical biology · 2017Review
- Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
There has been considerable interest in the use of antimicrobial peptides (AMPs) as antimicrobial agents for the treatment of many conditions, including cystic fibrosis (CF). The challenging conditions of the CF patient lung require robust AMPs that are active in an environment of high proteolytic activity but that also have low cytotoxicity and immunogenicity. Previously, we developed prodrugs of AMPs that limited the cytotoxic effects of AMP treatment by rendering the antimicrobial activity dependent on the host enzyme neutrophil elastase (NE). However, cytotoxicity remained an issue. Here, we describe the further optimization of the AMP prodrug (pro-AMP) model for CF to produce pro-WMR, a peptide with greatly reduced cytotoxicity (50% inhibitory concentration against CFBE41o- cells, >300 μM) compared to that of the previous group of pro-AMPs. The bactericidal activity of pro-WMR was increased in NE-rich bronchoalveolar lavage (BAL) fluid from CF patients (range, 8.4% ± 6.9% alone to 91.5% ± 5.8% with BAL fluid; P = 0.0004), an activity differential greater than that of previous pro-AMPs. In a murine model of lung delivery, the pro-AMP modification reduced host toxicity, with pro-WMR being less toxic than the active peptide. Previously, host toxicity issues have hampered the clinical application of AMPs. However, the development of application-specific AMPs with modifications that minimize toxicity similar to those described here can significantly advance their potential use in patients. The combination of this prodrug strategy with a highly active AMP has the potential to produce new therapeutics for the challenging conditions of the CF patient lung.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.