Garcinia benzophenones promote hyphal apoptosis and potentiate activity of fluconazole in C. albicans biofilms

Antimicrob Agents Chemother. 2015 Jul 20. pii: AAC.00820-15. [Epub ahead of print]


Xanthochymol and garcinol, isoprenylated benzophenones purified from Garcinia xanthochymus fruits, showed multiple activities against Candida albicans biofilms. Both compounds effectively prevented emergence of fungal germ tubes and were also cytostatic with MIC = 1-3 μM. The compounds therefore inhibited development of hyphae and subsequent biofilm maturation. Xanthochymol treatment of developing and mature biofilms induced cell death. In early biofilm development, killing had the characteristics of apoptosis, including externalization of phosphatydyl serine and DNA fragmentation as evidenced by TUNEL fluorescence. These activities resulted in failure of biofilm maturation and hyphal death in mature biofilms. In mature biofilms xanthochymol and garcinol caused death of biofilm hyphae with EC50 30-50 μM. Additionally, xanthochymol-mediated killing was complementary with fluconazole against mature biofilms, reducing the fluconazole EC50 value from >1024 μg/ml to 13 μg/ml. Therefore xanthochymol has potential as an adjuvant for antifungal treatments as well as in studies of fungal apoptosis.