title: Inhibition of the NorA multi-drug transporter by oxygenated monoterpenes.
abstract: The aim of this study was to investigate intrinsic antimicrobial activity of three monoterpenes nerol, dimethyl octanol and estragole, against bacteria and yeast strains, as well as, investigate if these compounds are able to inhibit the NorA efflux pump related to fluoroquinolone resistance in Staphylococcus aureus. Minimal inhibitory concentrations (MICs) of the monoterpenes against Staphylococcus aureus, Escherichia coli and Candida albicans strains were determined by micro-dilution assay. MICs of the norfloxacin against a S. aureus strain overexpressing the NorA protein were determined in the absence or in the presence of the monoterpenes at subinhibitory concentrations, aiming to verify the ability of this compounds act as efflux pump inhibitors. The monoterpenes were inactive against S. aureus however the nerol was active against E. coli and C. albicans. The addition of the compounds to growth media at sub-inhibitory concentrations enhanced the activity of norfloxacin against S. aureus SA1199-B. This result shows that bioactives tested, especially the nerol, are able to inhibit NorA efflux pump indicating a potential use as adjuvants of norfloxacin for therapy of infections caused by multi-drug resistant S. aureus strains.
authors: Laboratory of Toxicology Genetic Research, Federal University of Piauí, Teresina, Piauí, Brazil.
authors: Mayara Ladeira
authors: ML
authors: Coêlho
authors: Laboratory of Research in Microbiology, Federal University of Piauí, Teresina, PI, Brazil.
authors: Josie Haydée Lima
authors: JH
authors: Ferreira
authors: Laboratory of Genetics of Microorganisms, Federal University of Paraiba, João Pessoa, Paraiba, Brazil.
authors: José Pinto
authors: JP
authors: de Siqueira Júnior
authors: The John D. Dingell Department of Veteran's Affairs Medical Center, Detroit, MI, USA; Department of Internal Medicine, Division of Infectious Diseases, Wayne State University, Detroit, MI, USA.
authors: Glenn W
authors: GW
authors: Kaatz
authors: Laboratory of Research in Microbiology, Federal University of Piauí, Teresina, PI, Brazil. Electronic address: hmbarreto@ufpi.edu.br.
authors: Humberto Medeiros
authors: HM
authors: Barreto
authors: Laboratory of Toxicology Genetic Research, Federal University of Piauí, Teresina, Piauí, Brazil.
authors: Ana Amélia
authors: AA
authors: de Carvalho Melo Cavalcante
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors*; D002176:Candida albicans / Q000187:drug effects; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000378:metabolism*; D004926:Escherichia coli / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D039821:Monoterpenes / Q000378:metabolism*; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000037:antagonists & inhibitors*; D009643:Norfloxacin / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000201:enzymology*
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D004791:Enzyme Inhibitors; D039821:Monoterpenes; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009643:Norfloxacin; C075040:NorA protein, Staphylococcus
keywords: Bacterial resistance; Efflux pump inhibitor; Fluoroquinolone; Monoterpene; NorA