Premium
Synergistic activity of magnolol with azoles and its possible antifungal mechanism against C andida albicans
Author(s) -
Sun L.M.,
Liao K.,
Liang S.,
Yu P.H.,
Wang D.Y.
Publication year - 2015
Publication title -
journal of applied microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.889
H-Index - 156
eISSN - 1365-2672
pISSN - 1364-5072
DOI - 10.1111/jam.12737
Subject(s) - magnolol , candida albicans , efflux , ergosterol , microbiology and biotechnology , multiple drug resistance , biology , pharmacology , corpus albicans , azole , miconazole , fluconazole , atp binding cassette transporter , chemistry , drug resistance , biochemistry , transporter , antifungal , gene
Aim The goal of this study was to investigate the synergic effects between magnolol and azoles, and the potential antifungal mechanisms. Methods and Results Microdilution checkerboard, time‐kill and agar diffusion assay were employed to evaluate the synergic effects between magnolol and fluconazole ( FLC ). Magnolol significantly decreased the efflux of rhodamine 123 (Rh123), leading to greater intracellular accumulation of Rh123 in Candida albicans cells. Compared to the Candida drug resistance ( cdr ) 2 or multidrug resistance ( mdr ) 1 deletion mutant, the growth of cdr1 strain was most sensitive to magnolol exposure. In the presence of magnolol, MDR 1 overexpressing cells were sensitive to FLC , whereas CDR 1 and CDR 2 overexpressing cells displayed tolerance to FLC . Magnolol treatment correlated with up‐regulation of transporter and ergosterol biosynthesis pathway genes, analyzed by real‐time reverse transcription‐polymerase chain reaction. The ergosterol content of C. albicans SC 5314 was significantly decreased after magnolol exposure. Conclusions Magnolol synergizes with azoles for targeting of C. albicans by inducing a higher intracellular content of antifungals, by tapping into the competitive effect of ABC transporter Cdr1p substrates, and enhancing the effect by targeting of the ergosterol biosynthesis pathway. Significance and Impact of the Study Our results provide the first evidence that magnolol may function as a Cdr1p substrate and as an inhibitor of ergosterol biosynthesis. This function can thus be exploited in combination with azoles to reverse multidrug resistance of C. albicans strains.