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Study On The Screening Of Antifungal Natural Products And Molecular Mechanism

Posted on:2007-09-22Degree:DoctorType:Dissertation
Country:ChinaCandidate:J D ZhangFull Text:PDF
GTID:1104360185457117Subject:Pharmacology
Abstract/Summary:PDF Full Text Request
In recent twenty years, the risk of opportunistic fungal infections has greatly increased in patients. We have screened 328 natural products. Especially, we used bioassay-guided fractionation to have isolated steroid saponins, TTS-12, from Tribulus terrestris L., which showed very effective activities against pathogenic candidal species in vitro and in vivo, and haved lower toxicity in vivo. The ultrastructure, spectra data and sterol components wered effected by TTS-12, which pattern were identical with the results by Amphotericin A. Genome-wide transcript profiling following TTS-12 exposure was similar as that of AMB and nystatin, and ERG genes were suppressed and cellular transport genes were induced. Finally, proteomics profiling also showed several cellular transport proteins in the membrane induced by TTS-12. In conclusion, the mechanism of TTS-12 against Candida albicans should be that TTS-12 could bind to sterol in the membrane and cause the formation of cell membrane pores, leading to leakage of cell components.
Keywords/Search Tags:Candida albicans, Natural product, Saponins, Microarray, Proteomics
PDF Full Text Request
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