title: The activity of 16 new hydantoin compounds on the intrinsic and overexpressed efflux pump system of Staphylococcus aureus.
abstract: OBJECTIVE
  To evaluate a new series of 16 hydantoin derivatives for activity against the intrinsic and overexpressed efflux pumps of the ATTC 25923 Staphylococcus aureus and the clinical Staphylococcus aureus HPV-107 strain, respectively.
  
  
  METHODS
  The hydantoin compounds were evaluated for activity against the efflux pumps of the ATTC 25923 S. aureus and the clinical S. aureus HPV-107 strains by the aid of the automated ethidium bromide method. Compounds that inhibited the efflux pumps of either strain were evaluated for ability to reduce or reverse resistance of these strains to oxacillin.
  
  
  RESULTS
  Although most of the hydantoins inhibited the efflux pumps of the ATTC strain, none reduced the resistance of this strain to oxacillin. In contrast, the inhibition of the Qac efflux pump present in HPV-107 was inhibited to some degree, by much higher concentrations of the hydantoin compounds than that needed for similar activity against the ATTC strain; only hydantoin PI8a significantly reduced the minimum inhibitory concentration of oxacillin against the HPV-107 strain.
  
  
  CONCLUSIONS
  Hydantoin compound PI8a may have potential for therapy of a methicillin-resistant S. aureus infection whose multidrug-resistant phenotype is due to overexpression of an efflux pump.
authors.affiliation: Department of Technology and Biotechnology of Drugs, Jagiellonian University, Medical College, Krakow, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Dymek
authors.forename: Ana
authors.initials: A
authors.lastname: Armada
authors.forename: Jadwiga
authors.initials: J
authors.lastname: Handzlik
authors.forename: Miguel
authors.initials: M
authors.lastname: Viveiros
authors.forename: Gabriella
authors.initials: G
authors.lastname: Spengler
authors.forename: Joseph
authors.initials: J
authors.lastname: Molnar
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Kieć-Kononowicz
authors.forename: Leonard
authors.initials: L
authors.lastname: Amaral
mesh_terms: D001426:Bacterial Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D001692:Biological Transport / Q000187:drug effects*; D003199:Computer Systems; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects*; D004996:Ethidium / Q000378:metabolism; D005456:Fluorescent Dyes / Q000378:metabolism; D006827:Hydantoins / Q000494:pharmacology*; D026901:Membrane Transport Proteins / Q000378:metabolism; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D010068:Oxacillin / Q000378:metabolism / Q000494:pharmacology*; D010403:Penicillin Resistance / Q000187:drug effects; D010957:Plasmids / Q000235:genetics; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D005456:Fluorescent Dyes; D006827:Hydantoins; D026901:Membrane Transport Proteins; C099272:QacB protein, Staphylococcus aureus; C068498:qacA protein, Staphylococcus aureus; D004996:Ethidium; D010068:Oxacillin