Combinatorial activity of flavonoids with antibiotics against drug resistant Staphylococcus aureus

The use of resistance-modifying agents is a potential strategy that is used to prolong the effective life of antibiotics in the face of increasing antibiotic resistance. Since certain flavonoids are potent bacterial efflux pump inhibitors, we assessed morin, rutin, quercetin, hesperidin, and (+)-catechin for their combined activity with the antibiotics ciprofloxacin, tetracycline, erythromycin, oxacillin, and ampicillin against drug-resistant strains of Staphylococcus aureus, including methicillin-resistant S. aureus. Four established methods were used to determine the combined efficacy of each combination: microdilution checkerboard assays, time-kill determinations, the Etest, and dual disc-diffusion methods. The cytotoxicity of the flavonoids was additionally evaluated in a mouse fibroblast cell line. Quercetin and its isomer morin decreased by 3- to 16-fold the minimal inhibitory concentration of ciprofloxacin, tetracycline, and erythromycin against some S. aureus strains. Rutin, hesperidin, and (+)-catechin did not promote any potentiation of antibiotics. Despite the potential cytotoxicity of these phytochemicals at a high concentration (fibroblast IC50 of 41.8 and 67.5mg/L, respectively), quercetin is commonly used as a supplement for several therapeutic purposes. All the methods, with exception of the time-kill assay, presented a high degree of congruence without any apparent strain specificity.This work was supported by Operational Program for Competitiveness Factors—COMPETE, FCT/MEC (PIDDAC), and FEDER through Projects Bioresist—PTDC/EBB-EBI/ 105085/2008; Phytodisinfectants—PTDC/DTP-SAP/1078/ 2012 (COMPETE: FCOMP-01-0124-FEDER-028765) and the PhD grants awarded to Ana Abreu (SFRH/BD/84393/ 2012) and Anabela Borges (SFRH/BD/63398/2009). The authors are very grateful to Professor Simon Gibbons (De- partment of Pharmaceutical and Biological Chemistry, The School of Pharmacy, UCL School of Pharmacy, London) for providing the bacterial strains.info:eu-repo/semantics/publishedVersio

A systematic approach to the interrogation and sharing of standardised biofilm signatures

Publicado em "6th International Conference on Practical Applications of Computational Biology & Bioinformatics", ISBN 978-3-642-28838-8The study of microorganism consortia, also known as biofilms, is associated to a number of applications in biotechnology, ecotechnology and clinical domains. A public repository on existing biofilm studies would aid in the design of new studies as well as promote collaborative and incremental work. However, bioinformatics approaches are hampered by the limited access to existing data. Scientific publications summarise the studies whilst results are kept in researchers’ private ad hoc files. Since the collection and ability to compare existing data is imperative to move forward in biofilm analysis, the present work has addressed the development of a systematic computer-amenable approach to biofilm data organisation and standardisation. A set of in-house studies involving pathogens and employing different state-of-the-art devices and methods of analysis was used to validate the approach. The approach is now supporting the activities of BiofOmics, a public repository on biofilm signatures (http://biofomics.org).The authors thank, among others, Rosario Oliveira, Maria Joao Vieira, Idalina Machado, Nuno Cerca, Mariana Henriques, Pilar Teixeira, Douglas Monteiro, Melissa Negri, Susana Lopes, Carina Almeida and Helder Lopes, for submitting their data. The financial support from IBB-CEB, Fundacao para a Ciencia e Tecnologia (FCT) and European Community fund FEDER (Program COMPETE), project PTDC/SAU-ESA/646091/2006/FCOMP-01-0124-FEDER-007480, are also gratefully acknowledged