Retigeric Acid B Attenuates the Virulence of Candida albicans via Inhibiting Adenylyl Cyclase Activity Targeted by Enhanced Farnesol Production

Rab Fungal protein Virulence factor
DOI: 10.1371/journal.pone.0041624 Publication Date: 2012-07-23T21:40:34Z
ABSTRACT
Candida albicans, the most prevalent fungal pathogen, undergoes yeast-to-hyphal switch which has long been identified as a key virulence factor. We showed here that lichen-derived small molecule retigeric acid B (RAB) acted an inhibitor significantly inhibited filamentation of C. leading to prolonged survival nematodes infected by albicans. Quantitative real-time PCR analysis and intracellular cAMP measurement revealed RAB regulated Ras1-cAMP-Efg1 pathway reducing level inhibit hyphae formation. Confocal microscopic observation induced expression Dpp3, synthesizing more farnesol, was confirmed gas chromatography-mass spectroscopy detection. An adenylyl cyclase activity assay demonstrated could repress Cdc35 through stimulating farnesol synthesis, thus causing decrease in retarded transition. Moreover, reduced levels resulted inhibition downstream adhesins. Together, these findings indicate stimulates production directly inhibits activity, synthesis thereby disruption morphologic transition attenuating Our work illustrates underlying mechanism RAB-dependent provides potential application treating infection
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