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Chang, W./ Y. Li/ L. Zhang/ A. Cheng/ Y. Liu/ H. Lou 2012: Retigeric acid B enhances the efficacy of azoles combating the virulence and biofilm formation of Candida albicans. - Biological and Pharmaceutical Bulletin 35(10): 1794-1801. [RLL List # 231 / Rec.# 34632]
Keywords: Biofilm/ Candida albicans/ Hyphae/ Synergistic/ Virulence/ fluconazole/ itraconazole/ ketoconazole/ multidrug resistance protein 1/ retigeric acid B/ triterpenoid/ unclassified drug/ animal experiment/ animal model/ animal tissue/ antifungal activity/ article/ biofilm/ Candida albicans/ candidiasis/ CDR1 gene/ cell invasion/ combination chemotherapy/ controlled study/ drug efficacy/ drug potentiation/ fungal virulence/ fungus hyphae/ gene/ genetic transcription/ host pathogen interaction/ in vitro study/ in vivo study/ male/ MDR1 gene/ monotherapy/ mouse/ nonhuman/ Animals/ Antifungal Agents/ Biofilms/ Caco-2 Cells/ Candida albicans/ Candidiasis/ Drug Synergism/ Fluconazole/ Fungal Proteins/ Humans/ Itraconazole/ Ketoconazole/ Male/ Membrane Transport Proteins/ Mice/ Mice, Inbred BALB C/ P-Glycoprotein/ Triterpenes/ Virulence
Abstract: Candida albicans is one of the most prevalent human opportunistic pathogens. C. albicans undergoes a yeast-to-hyphal transition that has been identified as a virulence factor as well as a critical element for mature biofilm formation. A previous study in our lab showed retigeric acid B (RAB), a lichen derived pentacyclic triterpenoid, displayed synergistic antifungal activity with azoles. We now showed that this combination also proved to be adequate in combating the formation of hyphae in vitro. In vivo tests with mice demonstrated RAB could markedly enhance the efficacy of fluconazole to promote the host's longevity through inhibiting hyphae formation and adherence to host cells. It was also observed that RAB and azoles interacted synergistically to block the formation of biofilm. Our data suggested the attenuated yeast-to-hyphal switch contributed to the defect of mature biofilm formation. Moreover, quantitative real-time polymerase chain reaction (qPCR) analysis showed RAB could reduce the transcript level of MDR1, a multidrug efflux pump, and caused a slight transcriptional reduction for another drug pump related gene CDR1. Taken together, our work provides a potential application to combat candidiasis using the combination of RAB and azoles. © 2012 The Pharmaceutical Society of Japan.
Notes: Retigeric acid B (RAB) is a lichen derived pentacyclic triterpenoid.
URL: http://dx.doi.org/10.1248/bpb.b12-00511
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