Retigeric acid B enhances the efficacy of azoles combating the virulence and biofilm formation of Candida albicans.

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.

• Authors: Wenqiang Chang, Ying Li, Li Zhang, Aixia Cheng, Yongqing Liu, Hongxiang Lou
• Journal: Biological & pharmaceutical bulletin (Biol Pharm Bull) Vol. 35 Issue 10 Pg. 1794-801 ( 2012) ISSN: 1347-5215 [Electronic] Japan
• PMID: 22863995 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• ATP Binding Cassette Transporter, Subfamily B, Member 1
• Antifungal Agents
• CDR1 protein, Candida albicans
• Fungal Proteins
• Membrane Transport Proteins
• Triterpenes
• retigeric acid B
• Itraconazole
• Fluconazole
• Ketoconazole

Topics

• ATP Binding Cassette Transporter, Subfamily B, Member 1 (genetics)
• Animals
• Antifungal Agents (administration & dosage)
• Biofilms (drug effects)
• Caco-2 Cells
• Candida albicans (drug effects, pathogenicity, physiology)
• Candidiasis (drug therapy, microbiology)
• Drug Synergism
• Fluconazole (administration & dosage)
• Fungal Proteins (genetics)
• Humans
• Itraconazole (administration & dosage)
• Ketoconazole (administration & dosage)
• Male
• Membrane Transport Proteins (genetics)
• Mice
• Mice, Inbred BALB C
• Triterpenes (administration & dosage)
• Virulence (drug effects)