In Vitro Screening of an FDA-Approved Library Against ESKAPE Pathogens

Curr Pharm Des. 2017;23(14):2147-2157. doi: 10.2174/1381612823666170209154745.

Abstract

Bacterial resistance to conventional antibiotics is an increasingly serious threat to public health worldwide that requires immediate exploration and the development of novel antimicrobial compounds. Drug repurposing is an inexpensive and untapped source of new antimicrobial leads, and it holds many attractive features warranting further attention for antimicrobial drug discovery. In an effort to repurpose drugs and explore new leads in the field of antimicrobial drug discovery, we performed a whole-cell screening assay of 1,600 Food and Drug Administration (FDA) approved drugs against Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter cloacae (ESKAPE) pathogens. The in vitro screening identified 49 non-antimicrobial drugs that were active against at least one species of ESKAPE pathogen. Although some of these drugs were known to have antibacterial activity, many have never been reported before. In particular, sulfonamide-containing structures represent a novel drug scaffold that should be investigated further. The characteristics of these drugs as antimicrobial agents may offer a safe, effective, and quick supplement to current approaches to treating bacterial infections.

Keywords: ESKAPE; Repurposing; antibiotics; antimicrobial; repositioning.

MeSH terms

  • Acinetobacter baumannii / drug effects
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Anti-Bacterial Agents / standards
  • Dose-Response Relationship, Drug
  • Drug Approval / legislation & jurisprudence*
  • Enterobacter cloacae / drug effects
  • Enterococcus faecium / drug effects
  • Humans
  • Klebsiella pneumoniae / drug effects
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Pseudomonas aeruginosa / drug effects
  • Small Molecule Libraries / chemistry
  • Small Molecule Libraries / pharmacology*
  • Small Molecule Libraries / standards*
  • Staphylococcus aureus / drug effects
  • Structure-Activity Relationship
  • United States
  • United States Food and Drug Administration / legislation & jurisprudence*

Substances

  • Anti-Bacterial Agents
  • Small Molecule Libraries