Journal
MEDICAL MYCOLOGY
Volume 48, Issue 4, Pages 606-612Publisher
OXFORD UNIV PRESS
DOI: 10.3109/13693780903426721
Keywords
Candida; biofilm; Hsp90; voriconazole; micafungin
Categories
Funding
- KAKENHI [20591212, 20790714]
- Japan Health Science Foundation [KHC3333]
- [H20shinkouippann012]
- [H20nanchiippan035]
- [H20shinkouippan015]
- Grants-in-Aid for Scientific Research [20790714, 20591212] Funding Source: KAKEN
Ask authors/readers for more resources
We have conducted an in vitro evaluation of the efficacy of a voriconazole-micafungin combination against Candida albicans. When used alone, both micafungin and voriconazole decreased the metabolic activity of planktonic cells, but only micafungin displayed potent anti-biofilm activity. Their combination appeared to have an additive effect against planktonic cells. However, voriconazole significantly antagonized the fungicidal effect of micafungin against Candida biofilms. Time-lag experiments showed that pretreatment with voriconazole induced resistance to micafungin in Candida biofilms. The micafungin-antagonizing effect of voriconazole persisted even when the biofilm was no longer exposed to voriconazole. In contrast, voriconazole addition after 24 h of micafungin treatment did not alter micafungin sensitivity. To investigate the mechanism of antagonism, we used inhibitors of Hsp90 and its effectors because Hsp90 seems to be implicated in the resistance to micafungin. These molecules reversed the voriconazole-induced resistance to micafungin which suggests that Hsp90-related stress responses are involved in the antagonism. Our results may provide clues as to the mechanism of increased drug resistance in Candida biofilms and raises concerns about the use of the voriconazole-micafungin combination in clinical settings.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available