ArticleAntimicrobial agents and chemotherapy2015
Insect-derived cecropins display activity against Acinetobacter baumannii in a whole-animal high-throughput Caenorhabditis elegans model.
Article in Antimicrobial agents and chemotherapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed.
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- A novel broad-spectrum antibacterial and anti-malarial Anopheles gambiae Cecropin promotes microbial clearance during pupation.PLoS pathogens · 2024Article
- Alternatives to animal models to study bacterial infections.Folia microbiologica · 2023Review
- An Update on the Therapeutic Potential of Antimicrobial Peptides againstPharmaceuticals (Basel, Switzerland) · 2023Review
- Hirudomacin: a Protein with Dual Effects of Direct Bacterial Inhibition and Regulation of Innate Immunity.Applied and environmental microbiology · 2023Article
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- Antimicrobial Peptide Cec4 Eradicates Multidrug-ResistantDrug design, development and therapy · 2023Article
- Evidence for Complex Interplay between Quorum Sensing and Antibiotic Resistance in Pseudomonas aeruginosa.Microbiology spectrum · 2022Article
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- Mechanistic insights into synergy between nalidixic acid and tetracycline against clinical isolates of Acinetobacter baumannii and Escherichia coli.Communications biology · 2021Article
- Antimicrobial Peptides: Novel Source and Biological Function With a Special Focus on Entomopathogenic Nematode/Bacterium Symbiotic Complex.Frontiers in microbiology · 2021Review
- Identification of a Novel Cathelicidin from theToxins · 2020Article
- Antibacterial Activity of a Cationic Antimicrobial Peptide against Multidrug-Resistant Gram-Negative Clinical Isolates and Their Potential Molecular Targets.Molecules (Basel, Switzerland) · 2020Article
- Anti-MRSA agent discovery using Caenorhabditis elegans-based high-throughput screening.Journal of microbiology (Seoul, Korea) · 2020Review
- A VersaTile-driven platform for rapid hit-to-lead development of engineered lysins.Science advances · 2020Article
- A Novel Cecropin D-Derived Short Cationic Antimicrobial Peptide Exhibits Antibacterial Activity Against Wild-Type and Multidrug-Resistant Strains ofEvolutionary bioinformatics online · 2020Article
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Authors and funding
8 authors.
Funding
Abstract
The rise of multidrug-resistant Acinetobacter baumannii and a concomitant decrease in antibiotic treatment options warrants a search for new classes of antibacterial agents. We have found that A. baumannii is pathogenic and lethal to the model host organism Caenorhabditis elegans and have exploited this phenomenon to develop an automated, high-throughput, high-content screening assay in liquid culture that can be used to identify novel antibiotics effective against A. baumannii. The screening assay involves coincubating C. elegans with A. baumannii in 384-well plates containing potential antibacterial compounds. At the end of the incubation period, worms are stained with a dye that stains only dead animals, and images are acquired using automated microscopy and then analyzed using an automated image analysis program. This robust assay yields a Z' factor consistently greater than 0.7. In a pilot experiment to test the efficacy of the assay, we screened a small custom library of synthetic antimicrobial peptides (AMPs) that were synthesized using publicly available sequence data and/or transcriptomic data from immune-challenged insects. We identified cecropin A and 14 other cecropin or cecropin-like peptides that were able to enhance C. elegans survival in the presence of A. baumannii. Interestingly, one particular hit, BR003-cecropin A, a cationic peptide synthesized by the mosquito Aedes aegypti, showed antibiotic activity against a panel of Gram-negative bacteria and exhibited a low MIC (5 μg/ml) against A. baumannii. BR003-cecropin A causes membrane permeability in A. baumannii, which could be the underlying mechanism of its lethality.
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