Synergistic mechanisms of retigeric acid B and azoles against Candida albicans.
OBJECTIVE
To clarify the underlying synergistic antifungal mechanisms of retigeric acid B (RAB) in combination with azoles against Candida albicans.


RESULTS
Increased accumulation of rhodamine 123 in C. albicans was measured by both spectrophotometric method and flow cytometry. The inhibitory properties to the drug efflux of C. albicans were determined spectrophotometrically. The decreased cellular ergosterol synthesis was measured using its unique spectrophotometric absorbance profile, and the downregulation expression levels of CDR1 and ERG11 were detected by real-time reverse transcription polymerase chain reaction. Transmission electron microscopy investigation found the wrinkled cell membrane and the impaired cell wall.


CONCLUSIONS
RAB synergizes the antifungal effect of azoles against C. albicans by inhibiting efflux pump activity, targeting the ergosterol biosynthesis pathway and increasing the fluidity for the resulted ergosterol depletion.


CONCLUSIONS
Investigating the mechanism of the synergy between RAB and azoles against C. albicans will help us to uncover the antifungal roles of this lichen-derived triterpene acid and find its possible clinical applications in overcoming fungal resistance.
Sun
L M
LM
School of Pharmaceutical Sciences, Shandong University, Jinan, China.
Cheng
A X
AX
Wu
X Z
XZ
Zhang
H J
HJ
Lou
H X
HX
D000890:Anti-Infective Agents / Q000494:pharmacology*; D001393:Azoles / Q000819:agonists* / Q000494:pharmacology*; D002176:Candida albicans / Q000254:growth & development* / Q000378:metabolism / Q000648:ultrastructure; D002462:Cell Membrane / Q000378:metabolism / Q000648:ultrastructure; D004357:Drug Synergism; D004875:Ergosterol / Q000096:biosynthesis; D005656:Fungal Proteins / Q000096:biosynthesis; D015966:Gene Expression Regulation, Fungal / Q000187:drug effects; D026901:Membrane Transport Proteins / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D014315:Triterpenes / Q000819:agonists* / Q000494:pharmacology*
D000890:Anti-Infective Agents; D001393:Azoles; C094693:CDR1 protein, Candida albicans; D005656:Fungal Proteins; D026901:Membrane Transport Proteins; D014315:Triterpenes; C540615:retigeric acid B; D004875:Ergosterol