ArticlePloS one2014
Whole animal automated platform for drug discovery against multi-drug resistant Staphylococcus aureus.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
58 citing papers in PubMed, 99 citations in OpenAlex.
- Article
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- Assessment of carvacrol-antibiotic combinations' antimicrobial activity against methicillin-resistantFrontiers in microbiology · 2023Article
- Gold complex compounds that inhibit drug-resistantFrontiers in antibiotics · 2023Article
- High-throughput screening strategies for space-based radiation countermeasure discovery.Life sciences in space research · 2022Review
- Library Screening for Synergistic Combinations of FDA-Approved Drugs and Metabolites with Vancomycin against VanA-Type Vancomycin-Resistant Enterococcus faecium.Microbiology spectrum · 2022Article
- Closantel is an allosteric inhibitor of human Taspase1.iScience · 2021Article
- Quantitative behavioural phenotyping to investigate anaesthesia induced neurobehavioural impairment.Scientific reports · 2021Article
- Using membrane perturbing small molecules to target chronic persistent infections.RSC medicinal chemistry · 2021Review
- Drug discovery: Insights from the invertebrate Caenorhabditis elegans.Pharmacology research & perspectives · 2021Review
- Novel Immune Modulators EnhancemSphere · 2021Article
- Bio-evaluation of fluoro and trifluoromethyl-substituted salicylanilides against multidrug-resistantMedicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2021Article
- Thioredoxin Reductase Is a Valid Target for Antimicrobial Therapeutic Development Against Gram-Positive Bacteria.Frontiers in microbiology · 2021Article
- EML webinar overview: Simulation-assisted discovery of membrane targeting nanomedicine.Extreme Mechanics Letters · 2020Article
- Characterization of Five Novel Anti-MRSA Compounds Identified Using a Whole-AnimalAntibiotics (Basel, Switzerland) · 2020Article
- Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
Staphylococcus aureus, the leading cause of hospital-acquired infections in the United States, is also pathogenic to the model nematode Caenorhabditis elegans. The C. elegans-S. aureus infection model was previously carried out on solid agar plates where the bacteriovorous C. elegans feeds on a lawn of S. aureus. However, agar-based assays are not amenable to large scale screens for antibacterial compounds. We have developed a high throughput liquid screening assay that uses robotic instrumentation to dispense a precise amount of methicillin resistant S. aureus (MRSA) and worms in 384-well assay plates, followed by automated microscopy and image analysis. In validation of the liquid assay, an MRSA cell wall defective mutant, MW2ΔtarO, which is attenuated for killing in the agar-based assay, was found to be less virulent in the liquid assay. This robust assay with a Z'-factor consistently greater than 0.5 was utilized to screen the Biomol 4 compound library consisting of 640 small molecules with well characterized bioactivities. As proof of principle, 27 of the 30 clinically used antibiotics present in the library conferred increased C. elegans survival and were identified as hits in the screen. Surprisingly, the antihelminthic drug closantel was also identified as a hit in the screen. In further studies, we confirmed the anti-staphylococcal activity of closantel against vancomycin-resistant S. aureus isolates and other Gram-positive bacteria. The liquid C. elegans-S. aureus assay described here allows screening for anti-staphylococcal compounds that are not toxic to the host.
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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.