title: Inhibition of the NorA efflux pump of Staphylococcus aureus by synthetic riparins.
abstract: OBJECTIVE
  The goal of this study was to increase knowledge about the antimicrobial activity of some synthetic Riparin-derived compounds, alone or in combination with fluoroquinolone antibiotics, against a strain of Staphylococcus aureus resistant to fluoroquinolone by way of overexpression of the NorA efflux pump.
  
  
  RESULTS
  Microdilution tests showed that Riparins A and B did not show any significant antibacterial activity against Staph. aureus strains. On the other hand, the intrinsic antibacterial activity increased with increasing lipophilicity of the compounds, in the following order: Riparin-D (MIC 256 μg ml-1; Log P 2·95) < Riparin-C (MIC 102 μg ml-1; Log P 3·22) < Riparin-E (MIC 16 μg ml-1; Log P 3·57). The addition of all riparins to growth media at subinhibitory concentrations caused an increase in the antibacterial activity of antibiotics against the NorA-overexpressing test strain. Riparin-B, which has two methoxyl groups at the phenethyl moiety, showed the best modulatory effect.
  
  
  CONCLUSIONS
  Riparin-E is a good anti-staphylococci agent, while Riparin-B functions as a NorA efflux pump inhibitor.
  
  
  CONCLUSIONS
  Our data suggest the possibility of using Riparin-B in combination with norfloxacin or ciprofloxacin for therapy of infections caused by multi-drug resistant Staph. aureus.
authors.affiliation: Laboratory for Research in Experimental Neurochemistry, Federal University of Piauí, Teresina (PI), Brazil.
authors.forename: L M
authors.initials: LM
authors.lastname: Costa
authors.affiliation: Laboratory for Research in Microbiology, Federal University of Piauí, Teresina (PI), Brazil.
authors.forename: E V
authors.initials: EV
authors.lastname: de Macedo
authors.affiliation: Laboratory for Research in Microbiology, Federal University of Piauí, Teresina (PI), Brazil.
authors.forename: F A A
authors.initials: FA
authors.lastname: Oliveira
authors.affiliation: Laboratory for Research in Microbiology, Federal University of Piauí, Teresina (PI), Brazil.
authors.forename: J H L
authors.initials: JH
authors.lastname: Ferreira
authors.affiliation: Laboratory for Research in Microbiology, Federal University of Piauí, Teresina (PI), Brazil.
authors.forename: S J C
authors.initials: SJ
authors.lastname: Gutierrez
authors.affiliation: INFIQC-CONICET, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Ciudad Universitaria, Córdoba, Argentina.
authors.forename: W J
authors.initials: WJ
authors.lastname: Peláez
authors.affiliation: Laboratory of Computational Quantum Chemistry and Drug Planning, State University of Piauí, Teresina (PI), Brazil.
authors.forename: F C A
authors.initials: FC
authors.lastname: Lima
authors.affiliation: Laboratory of Genetic of Microorganisms, Federal University of Paraiba, João Pessoa (PB), Brazil.
authors.forename: J P
authors.initials: JP
authors.lastname: de Siqueira Júnior
authors.affiliation: Laboratory of Microbiology and Molecular Biology, Regional University of Cariri, Crato (CE), Brazil.
authors.forename: H D M
authors.initials: HD
authors.lastname: Coutinho
authors.affiliation: Department of Medicine, Division of Infectious Diseases, Wayne State University School of Medicine, Detroit, MI, USA.
authors.forename: G W
authors.initials: GW
authors.lastname: Kaatz
authors.affiliation: Laboratory for Research in Experimental Neurochemistry, Federal University of Piauí, Teresina (PI), Brazil.
authors.forename: R M
authors.initials: RM
authors.lastname: de Freitas
authors.affiliation: Laboratory for Research in Microbiology, Federal University of Piauí, Teresina (PI), Brazil. hmbarreto@ufpi.edu.br.
authors.forename: H M
authors.initials: HM
authors.lastname: Barreto
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors*; D001549:Benzamides / Q000737:chemistry / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial; D024841:Fluoroquinolones / Q000494:pharmacology; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000037:antagonists & inhibitors*; D013211:Staphylococcus aureus / Q000187:drug effects*
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D001549:Benzamides; D024841:Fluoroquinolones; D027425:ATP-Binding Cassette, Sub-Family C Proteins; C075040:NorA protein, Staphylococcus
keywords: antibiotics; diseases; infection; resistance; staphylococci