title: Potent and selective inhibitors of Staphylococcus epidermidis tryptophanyl-tRNA synthetase.
abstract: OBJECTIVE
  The skin commensal and opportunistic pathogen Staphylococcus epidermidis is one of the leading causes of nosocomial and biofilm-associated infections, which urgently requires discovery of new antibiotics. We decided to find new leads that target the S. epidermidis tryptophanyl-tRNA synthetase (SeWRS), which is essential for translation.
  
  
  METHODS
  We applied an approach combining structure-based discovery in silico with biochemical and biological experiments in vitro to screen SeWRS inhibitors.
  
  
  RESULTS
  Three compounds have an inhibitory effect on enzymatic activities of SeWRS, of which two show low inhibition of the human tryptophanyl-tRNA synthetase. Binding of these compounds to bacterially expressed SeWRS was demonstrated by surface plasmon resonance technology. These three compounds can also obviously inhibit growth of S. epidermidis in vitro and displayed low cytotoxicity to mammalian cells.
  
  
  CONCLUSIONS
  These compounds are good leads to develop new antibiotics.
authors.affiliation: Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, Institute of Medical Microbiology and Institutes of Biomedical Sciences, Shanghai Medical School of Fudan University, Shanghai 200032, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Wu
authors.forename: Kunqian
authors.initials: K
authors.lastname: Yu
authors.forename: Bin
authors.initials: B
authors.lastname: Xu
authors.forename: Lili
authors.initials: L
authors.lastname: Chen
authors.forename: Xianglong
authors.initials: X
authors.lastname: Chen
authors.forename: Jialing
authors.initials: J
authors.lastname: Mao
authors.forename: Antoine
authors.initials: A
authors.lastname: Danchin
authors.forename: Xu
authors.initials: X
authors.lastname: Shen
authors.forename: Di
authors.initials: D
authors.lastname: Qu
authors.forename: Hualiang
authors.initials: H
authors.lastname: Jiang
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002522:Chlorocebus aethiops; D003470:Culture Media; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D008024:Ligands; D008826:Microbial Sensitivity Tests; D009391:Nephelometry and Turbidimetry; D011994:Recombinant Proteins / Q000737:chemistry; D013212:Staphylococcus epidermidis / Q000187:drug effects / Q000201:enzymology* / Q000254:growth & development; D020349:Surface Plasmon Resonance; D014369:Tryptophan-tRNA Ligase / Q000037:antagonists & inhibitors*; D014709:Vero Cells
chemical_list: D000900:Anti-Bacterial Agents; D003470:Culture Media; D004791:Enzyme Inhibitors; D008024:Ligands; D011994:Recombinant Proteins; D014369:Tryptophan-tRNA Ligase