An update on the use of C. elegans for preclinical drug discovery: screening and identifying anti-infective drugs

Expert Opin Drug Discov. 2017 Jun;12(6):625-633. doi: 10.1080/17460441.2017.1319358. Epub 2017 Apr 21.


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.

Keywords: Caenorhabditis elegans; antibiotics; drug discovery; high-throughput screen.

Publication types

  • Review

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology*
  • Anti-Bacterial Agents / toxicity
  • Bacteria / drug effects
  • Bacteria / genetics
  • Caenorhabditis elegans*
  • Drug Design
  • Drug Discovery / methods*
  • Drug Evaluation, Preclinical / methods
  • Drug Resistance, Bacterial
  • Gene Knockdown Techniques
  • High-Throughput Screening Assays / methods
  • Humans


  • Anti-Bacterial Agents