title: An update on the use of C. elegans for preclinical drug discovery: screening and identifying anti-infective drugs.
abstract: 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.
authors.affiliation: a Division of Infectious Diseases , Rhode Island Hospital, Alpert Medical School of Brown University , Providence , RI , USA.
authors.forename: Wooseong
authors.initials: W
authors.lastname: Kim
authors.affiliation: a Division of Infectious Diseases , Rhode Island Hospital, Alpert Medical School of Brown University , Providence , RI , USA.
authors.forename: Gabriel Lambert
authors.initials: GL
authors.lastname: Hendricks
authors.affiliation: a Division of Infectious Diseases , Rhode Island Hospital, Alpert Medical School of Brown University , Providence , RI , USA.
authors.forename: Kiho
authors.initials: K
authors.lastname: Lee
authors.affiliation: a Division of Infectious Diseases , Rhode Island Hospital, Alpert Medical School of Brown University , Providence , RI , USA.
authors.forename: Eleftherios
authors.initials: E
authors.lastname: Mylonakis
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000633:toxicity; D001419:Bacteria / Q000187:drug effects / Q000235:genetics; D017173:Caenorhabditis elegans; D015195:Drug Design; D055808:Drug Discovery / Q000379:methods*; D004353:Drug Evaluation, Preclinical / Q000379:methods; D024881:Drug Resistance, Bacterial; D055785:Gene Knockdown Techniques; D057166:High-Throughput Screening Assays / Q000379:methods; D006801:Humans
chemical_list: D000900:Anti-Bacterial Agents
keywords: Caenorhabditis elegans; antibiotics; drug discovery; high-throughput screen