title: In vitro and in vivo activities of pterostilbene against Candida albicans biofilms.
abstract: Pterostilbene (PTE) is a stilbene-derived phytoalexin that originates from several natural plant sources. In this study, we evaluated the activity of PTE against Candida albicans biofilms and explored the underlying mechanisms. In 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) reduction assays, biofilm biomass measurement, confocal laser scanning microscopy, and scanning electron microscopy, we found that ≤16 μg/ml PTE had a significant effect against C. albicans biofilms in vitro, while it had no fungicidal effect on planktonic C. albicans cells, which suggested a unique antibiofilm effect of PTE. Then we found that PTE could inhibit biofilm formation and destroy the maintenance of mature biofilms. At 4 μg/ml, PTE decreased cellular surface hydrophobicity (CSH) and suppressed hyphal formation. Gene expression microarrays and real-time reverse transcription-PCR showed that exposure of C. albicans to 16 μg/ml PTE altered the expression of genes that function in morphological transition, ergosterol biosynthesis, oxidoreductase activity, and cell surface and protein unfolding processes (heat shock proteins). Filamentation-related genes, especially those regulated by the Ras/cyclic AMP (cAMP) pathway, including ECE1, ALS3, HWP1, HGC1, and RAS1 itself, were downregulated upon PTE treatment, indicating that the antibiofilm effect of PTE was related to the Ras/cAMP pathway. Then, we found that the addition of exogenous cAMP reverted the PTE-induced filamentous growth defect. Finally, with a rat central venous catheter infection model, we confirmed the in vivo activity of PTE against C. albicans biofilms. Collectively, PTE had strong activities against C. albicans biofilms both in vitro and in vivo, and these activities were associated with the Ras/cAMP pathway.
authors: New Drug Research and Development Center, School of Pharmacy, Second Military Medical University, Shanghai, China.
authors: De-Dong
authors: DD
authors: Li
authors: Lan-Xue
authors: LX
authors: Zhao
authors: Eleftherios
authors: E
authors: Mylonakis
authors: Gan-Hai
authors: GH
authors: Hu
authors: Yong
authors: Y
authors: Zou
authors: Tong-Kun
authors: TK
authors: Huang
authors: Lan
authors: L
authors: Yan
authors: Yan
authors: Y
authors: Wang
authors: Yuan-Ying
authors: YY
authors: Jiang
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D018441:Biofilms / Q000187:drug effects*; D002176:Candida albicans / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology*; D005260:Female; D005656:Fungal Proteins / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D008855:Microscopy, Electron, Scanning; D051381:Rats; D017207:Rats, Sprague-Dawley; D013267:Stilbenes / Q000494:pharmacology* / Q000627:therapeutic use*
chemical_list: D000935:Antifungal Agents; D005656:Fungal Proteins; D013267:Stilbenes; C107773:pterostilbene