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Study On The Function Of Orf19.1034 In Candida Albicans

Posted on:2020-01-10Degree:MasterType:Thesis
Country:ChinaCandidate:M M WangFull Text:PDF
GTID:2404330572488454Subject:Microbiology
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Candida albicans is the most common condition pathogenic fungus of humans that is found in the skin,oral cavity,vagina and gastrointestinal tract.It can grow in several morphological forms including unicellular yeast-form,elongated hyphae and pseudohyphae,and the ability to switch between yeast and yeast-form is thought to be tightly linked with virulence.In the course of treatment,due to the extensive use of antificials,the drug-resistant strains of C.albicans are strengthened.Therefore,it is of great significance to study and reveal the pathogenic and drug resistance mechanism of C.albicans and develop new antifungal drugs for the treatment of C.albicans infection.Through sequence comparison,it was found that Orf19.1034 was homologous with ScDap1 in Saccharomy cescerevisiae and CgDap1 in Candida glabrata,with a common domain of cytochrome b5 in their gene sequence.The protein of Dap1 has been shown to be associated with the synthesis of ergosterol in S.cerevisiae and C.glabrata,which was an important component of biofilms,and was associated with the synthesis of sterol and the tolerance of antifungal drugs.Therefore,the design test was conducted to explore whether orf19.1034 was also involved in ergosterol synthesis pathway,so as to further explore new virulence factors and provide certain theoretical basis for the study of new antifungal drugs.Therefore,in this study,we have investigated the phenotypes in growth and hyphal development by means of gene knockout,phenotypes and mice.Based on the research in this paper,the following results can be obtained:1)The C.albicans cells lacking orf19.1034 were sensitive to the Cu2+,Sodium dodecyl sulfate?SDS?,Terbinafine?Teb?and Caspofungin?CSF?,and resistance to Congo red?CR?,Calcofluor white?CFW?,Fluconazole?Flu?and Ketoconazole?KCZ?;2)At the same drug concentration level,only the phenotypes of CSF and KCZ showed partial recovery after the addition of ergosterol.Indication that the sensitivity to CSF andKCZ drugs was related to the synthesis defect of ergosterol after gene deletion;3)After gene deletion,the content of chitin in the cell wall decteased;4)After gene deletion,hyphal development ability of C.albicans is impaired;5)orf19.1034 was associated with the virulence of C.albicans.Through the preliminary study of orf19.1034,the following conclusions can be drawn:The gene of orf19.1034 was involved in the chitin synthesis pathway in the cell wall,and the toxicity of C.albicans can be reduced after gene deletion.
Keywords/Search Tags:Candida albicans, Orf19.1034, Ergosterol, CFW, Hyphal formation, Virulence
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