title: Combinatorial approaches with selected phytochemicals to increase antibiotic efficacy against Staphylococcus aureus biofilms.
abstract: Combinations of selected phytochemicals (reserpine, pyrrolidine, quinine, morin and quercetin) with antibiotics (ciprofloxacin, tetracycline and erythromycin) were tested on the prevention and control of Staphylococcus aureus biofilms. The phytochemicals were also studied for their ability to avoid antibiotic adaptation and to inhibit antibiotic efflux pumps. Morin, pyrrolidine and quercetin at subinhibitory concentrations had significant effects in biofilm prevention and/or control when applied alone and combined with antibiotics. Synergism between antibiotics and phytochemicals was found especially against biofilms of NorA overexpressing strain S. aureus SA1199B. This strain when growing with subinhibitory concentrations of ciprofloxacin developed increased tolerance to this antibiotic. However, this was successfully reversed by quinine and morin. In addition, reserpine and quercetin showed significant efflux pump inhibition. The overall results demonstrate the role of phytochemicals in co-therapies to promote more efficient treatments and decrease antimicrobial resistance to antibiotics, with substantial effects against S. aureus in both planktonic and biofilm states.
authors.affiliation: a LEPABE, Department of Chemical Engineering, Faculty of Engineering , University of Porto , Porto , Portugal.
authors.forename: Ana Cristina
authors.initials: AC
authors.lastname: Abreu
authors.affiliation: b CECAV, Veterinary and Animal Science Research Center, Quality and Food Safety of Animal Products Group , University of Trás-os-Montes and Alto Douro , Vila Real , Portugal.
authors.forename: Maria José
authors.initials: MJ
authors.lastname: Saavedra
authors.affiliation: a LEPABE, Department of Chemical Engineering, Faculty of Engineering , University of Porto , Porto , Portugal.|c CEB - Centre of Biological Engineering , University of Minho , Braga , Portugal.
authors.forename: Lúcia C
authors.initials: LC
authors.lastname: Simões
authors.affiliation: a LEPABE, Department of Chemical Engineering, Faculty of Engineering , University of Porto , Porto , Portugal.
authors.forename: Manuel
authors.initials: M
authors.lastname: Simões
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects*; D002939:Ciprofloxacin / Q000008:administration & dosage / Q000494:pharmacology; D004357:Drug Synergism; D004917:Erythromycin / Q000008:administration & dosage / Q000494:pharmacology; D005419:Flavonoids / Q000008:administration & dosage / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D064209:Phytochemicals / Q000008:administration & dosage / Q000494:pharmacology*; D011794:Quercetin / Q000009:adverse effects / Q000494:pharmacology; D011803:Quinine / Q000008:administration & dosage / Q000494:pharmacology; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000502:physiology; D013752:Tetracycline / Q000008:administration & dosage / Q000494:pharmacology; D047309:Flavones
chemical_list: D000900:Anti-Bacterial Agents; D002939:Ciprofloxacin; D004917:Erythromycin; D005419:Flavonoids; D064209:Phytochemicals; D011794:Quercetin; D011803:Quinine; D013752:Tetracycline; C008548:morin; D047309:Flavones
keywords: Antibiotic adaptation; Staphylococcus aureus; antibiotic resistance; biofilms; efflux pump; phytochemicals