title: Evaluation of forty new phenothiazine derivatives for activity against intrinsic efflux pump systems of reference Escherichia coli, Salmonella Enteritidis, Enterococcus faecalis and Staphylococcus aureus strains.
abstract: BACKGROUND
  Because phenothiazines inhibit efflux pumps of bacteria, forty new phenothiazine derivatives were tested for their inhibition of the efflux pump systems of Gram-positive and Gram-negative pathogenic bacteria.
  
  
  METHODS
  Detection of efflux pump activity was conducted by a previously described automated fluorimetric method.
  
  
  RESULTS
  Although many of the compounds significantly inhibited efflux by distinct bacteria, four compounds had exceptional activity against the efflux pump systems of the pathogenic wild type bacteria Escherichia coli, Salmonella Enteritidis, Enterococcus faecalis and Staphylococcus aureus. These four compounds were then evaluated for ability to reduce or reverse resistance of multi-drug resistant members of Escherichia coli, Salmonella and Staphylococcus aureus whose MDR phenotypes are mediated by specific over-expressed efflux pumps. One of the compounds, 2173, significantly reduced resistance of MDR Staphylococcus aureus.
  
  
  CONCLUSIONS
  These results suggest possible use of compound 2173 for therapy of infections caused by this organism.
authors.affiliation: Unit of Mycobacteriology, Institute of Hygiene and Tropical Medicine, Rua da Junqueira 96, 1349-008 Lisboa, Portugal.
authors.forename: Daniella
authors.initials: D
authors.lastname: Takács
authors.forename: Pedro
authors.initials: P
authors.lastname: Cerca
authors.forename: Ana
authors.initials: A
authors.lastname: Martins
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Riedl
authors.forename: György
authors.initials: G
authors.lastname: Hajós
authors.forename: Joseph
authors.initials: J
authors.lastname: Molnár
authors.forename: Miguel
authors.initials: M
authors.lastname: Viveiros
authors.forename: Isabel
authors.initials: I
authors.lastname: Couto
authors.forename: Leonard
authors.initials: L
authors.lastname: Amaral
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000378:metabolism*; D024901:Drug Resistance, Multiple, Bacterial; D004357:Drug Synergism; D013293:Enterococcus faecalis / Q000187:drug effects* / Q000378:metabolism; D004926:Escherichia coli / Q000187:drug effects* / Q000378:metabolism; D004996:Ethidium / Q000378:metabolism; D005456:Fluorescent Dyes / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000378:metabolism*; D008826:Microbial Sensitivity Tests; D010068:Oxacillin / Q000494:pharmacology; D010640:Phenothiazines / Q000494:pharmacology*; D012477:Salmonella enteritidis / Q000187:drug effects* / Q000378:metabolism; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D005456:Fluorescent Dyes; D026901:Membrane Transport Proteins; D010640:Phenothiazines; D004996:Ethidium; D010068:Oxacillin