title: Natural product solasodine-3-O-β-D-glucopyranoside inhibits the virulence factors of Candida albicans.
abstract: Candida albicans undergoes yeast-to-hyphal transition that has been recognized as a virulence factor as well as the key point for the development of mature biofilm. In this study, we found that a natural product, solasodine-3-O-β-D-glucopyranoside (SG), a steroidal alkaloid glycoside, isolated from Solanum. nigrum L., could attenuate the virulence of C. albicans by inhibiting the adhesion and morphological transition. Moreover, SG dramatically inhibited the biofilm formation and displayed killing activity against the mature biofilm. In vivo study using Caenorhabditis elegans showed that SG prolonged the survival time of C. albicans infected worms. The mechanism investigation revealed that SG could inhibit the expression of adhesions and hyphae-specific genes by regulating Ras-cAMP-PKA signaling pathway. The inhibitory effects on yeast-to-hyphal conversion and biofilm formation caused by SG could be rescued by addition of exogenerous cAMP, suggesting that the retarded cAMP synthesis is responsible for these actions. Taken together, our work uncovers the underlying mechanism of SG-dependent inhibition of the yeast-to-hyphal switch and biofilm formation and provides a potential application in treating relevant fungal infections.
authors.affiliation: Department of Natural Product Chemistry, Key Lab of Chemical Biology of Ministry of Education, Shandong University, No. 44 West Wenhua Road, Jinan City, Shandong Province 250012, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Natural Product Chemistry, Key Lab of Chemical Biology of Ministry of Education, Shandong University, No. 44 West Wenhua Road, Jinan City, Shandong Province 250012, China.
authors.forename: Wenqiang
authors.initials: W
authors.lastname: Chang
authors.affiliation: Department of Natural Product Chemistry, Key Lab of Chemical Biology of Ministry of Education, Shandong University, No. 44 West Wenhua Road, Jinan City, Shandong Province 250012, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhang
authors.affiliation: School of Pharmaceutical Sciences, Taishan Medical University, Taian City, Shandong Province 271000, China.
authors.forename: Zhao
authors.initials: Z
authors.lastname: Ying
authors.affiliation: Department of Natural Product Chemistry, Key Lab of Chemical Biology of Ministry of Education, Shandong University, No. 44 West Wenhua Road, Jinan City, Shandong Province 250012, China louhongxiang@sdu.edu.cn.
authors.forename: Hongxiang
authors.initials: H
authors.lastname: Lou
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000302:isolation & purification / Q000378:metabolism*; D018441:Biofilms / Q000187:drug effects* / Q000254:growth & development; D001688:Biological Products / Q000302:isolation & purification / Q000378:metabolism*; D017173:Caenorhabditis elegans / Q000382:microbiology; D002176:Candida albicans / Q000187:drug effects* / Q000502:physiology; D000242:Cyclic AMP / Q000378:metabolism; D004195:Disease Models, Animal; D006027:Glycosides / Q000302:isolation & purification / Q000378:metabolism; D025301:Hyphae / Q000187:drug effects* / Q000254:growth & development; D050296:Microbial Viability / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D012991:Solanaceous Alkaloids / Q000302:isolation & purification / Q000378:metabolism*; D032322:Solanum / Q000737:chemistry; D016019:Survival Analysis; D037521:Virulence Factors / Q000037:antagonists & inhibitors*
chemical_list: D000935:Antifungal Agents; D001688:Biological Products; D006027:Glycosides; D012991:Solanaceous Alkaloids; D037521:Virulence Factors; D000242:Cyclic AMP; C012037:solasodine
keywords: Candida albicans; biofilm; hyphae; solasodine-3-O-β-D-glucopyranoside; virulence