Antibiotic adjuvants from Buxus sempervirens to promote effective treatment of drug-resistant Staphylococcus aureus biofilms

• Autor(a) principal: A. C. Abreu
• Data de Publicação: 2016
• Outros Autores: D. Paulet, A. Coqueiro, J. Malheiro, A. Borges, M. J. Saavedra, Y. H. Choi, M. Simões
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: https://hdl.handle.net/10216/103269
• topic: Ciências da Saúde, Ciências médicas e da saúde, Ciências da engenharia e tecnologias; Health sciences, Medical and Health sciences, Engineering and technology

Plants have been long scrutinized in the quest for new antibiotics, but no strong antibiotic molecule was ever found. Evidence exists that most phytochemicals have a regulatory or adjuvant effect on other antibacterial compounds, thus promoting a greater therapeutic effect. The current study assessed twenty-eight plants from different families for their antibacterial activity and as adjuvants in antibiotic therapy against Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA). Eucalyptus globulus, Castanea sativa, Agrimonia eupatoria and Fraxinus excelsior methanolic extracts showed antibacterial activity with minimal inhibitory concentrations (MICs) of 0.125-0.5, 0.5-1.0, 1.0-2.0, and 2.0-4.0 g L (1), respectively. Non-antibacterial plants were assessed in combination with ampicillin, oxacillin, ciprofloxacin, erythromycin and tetracycline by a modified disc diffusion test. Methanolic extracts of Acacia dealbata, Prunus spp. plants, Centaurea nigra, Eupatorium cannabium and Buxus sempervirens showed a potentiating effect mostly of ciprofloxacin, erythromycin and tetracycline. B. sempervirens was selected for its potentiating activity and applied against S. aureus biofilms. B. sempervirens (1 g L-1) was able to cause an 88% reduction of S. aureus within 1 h exposure. Further phytochemical investigation of B. sempervirens allowed to identify betulinic acid as a major component, together with other triterpenoids. Betulinic acid and other common terpernoids - lupeol, betulin, hederagenin, ursolic acid and oleanolic acid, were tested for antibacterial and antibiotic-potentiating activities. Among the tested compounds, oleanolic acid and ursolic acid - were highlighted, showing MIC of 62.5 and 15.6 mg L-1, respectively, against S. aureus. Additionally, oleanolic acid showed synergism when combined with tetracycline and erythromycin and caused biofilm reductions of 70, 81 and 85% when applied at 1/2 MIC, MIC and 2 x MIC, respectively.