An update on the use of C. elegans for preclinical drug discovery: screening and identifying anti-infective drugs. (3rd June 2017)

• Record Type: Journal Article
• Authors: Kim, Wooseong; Hendricks, Gabriel Lambert; Lee, Kiho; Mylonakis, Eleftherios
• Is Part Of: Expert opinion on drug discovery. Volume 12:Number 6(2017:Jun.)
• Page Start: 625
• Page End: 633
• Publication Date: 2017-06-03
• Subjects: Caenorhabditis elegans -- drug discovery -- high-throughput screen -- antibiotics; 615.1
• DOI: 10.1080/17460441.2017.1319358
• Languages: English
• ISSNs: 1746-0441

Abstract

ABSTRACT: Introduction : The emergence of antibiotic-resistant and -tolerant bacteria is a major threat to human health. Although efforts for drug discovery are ongoing, conventional bacteria-centered screening strategies have thus far failed to yield new classes of effective antibiotics. Therefore, new paradigms for discovering novel antibiotics are of critical importance. Caenorhabditis elegans, a model organism used for in vivo, offers a promising solution for identification of anti-infective compounds. Areas covered : This review examines the advantages of C. elegans-based high-throughput screening over conventional, bacteria-centered in vitro screens. It discusses major anti-infective compounds identified from large-scale C. elegans-based screens and presents the first clinically-approved drugs, then known bioactive compounds, and finally novel small molecules. Expert opinion : There are clear advantages of using a C. elegans-infection based screening method. A C. elegans-based screen produces an enriched pool of non-toxic, efficacious, potential anti-infectives, covering: conventional antimicrobial agents, immunomodulators, and anti-virulence agents. Although C. elegans-based screens do not denote the mode of action of hit compounds, this can be elucidated in secondary studies by comparing the results to target-based screens, or conducting subsequent target-based screens, including the genetic knock-down of host or bacterial genes.