Identification of small molecule compounds active against Staphylococcus aureus and Proteus mirabilis

Biochem Biophys Res Commun. 2018 Dec 2;506(4):1047-1051. doi: 10.1016/j.bbrc.2018.10.189. Epub 2018 Nov 5.

Abstract

Staphylococcus aureus is a human pathogen rapidly becoming a serious health problem due to ease of acquiring antibiotic resistance. To help identify potential new drug candidates effective against the pathogen, a small focused library was screened for inhibition of bacterial growth against several pathogens, including S. aureus. At least one of the compounds, Compound 10, was capable of blocking bacterial growth of S. aureus in a test tube with IC50 = 140 ± 30 μM. Another inhibitor, Compound 7, was bacteriostatic against S. aureus with IC50 ranging from 33 to 150 μM against 3 different strains. However, only Compound 7 was bactericidal against P. mirabilis as examined by electron microscopy. Human cell line toxicity studies suggested that both compounds had small effect on cell growth at 100 μM concentration as examined by MTT assay. Analysis of compounds' structures showed lack of similarity to any known antibiotics and bacteriostatics, potentially offering the inhibitors as an alternative to existing solutions in controlling bacterial infections for selected pathogens.

Keywords: ATPase; Antibiotic; Bacteriostatic; Electron microscopy; Proteus mirabilis; Staphylococcus aureus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • A549 Cells
  • Anti-Bacterial Agents / pharmacology*
  • Cell Survival / drug effects
  • Humans
  • Inhibitory Concentration 50
  • Microbial Sensitivity Tests
  • Microbial Viability / drug effects
  • Proteus mirabilis / drug effects*
  • Proteus mirabilis / growth & development
  • Proteus mirabilis / ultrastructure
  • Small Molecule Libraries / pharmacology*
  • Staphylococcus aureus / drug effects*
  • Staphylococcus aureus / growth & development
  • Staphylococcus aureus / ultrastructure

Substances

  • Anti-Bacterial Agents
  • Small Molecule Libraries