MOLECULAR GENETICS, BIOCHEMISTRY AND THERAPY OF CANDIDA ALBICANS

白色念珠菌的分子遗传学、生物化学和治疗

• 批准号: 5200552
• 负责人: J BENNETT
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/5200552
• 关键词: AIDS; Candida; Candida albicans; azoles; candidiasis; drug resistance; fungal genetics; gene deletion mutation; human subject; microorganism metabolism; northern blottings; nucleic acid sequence; relapse /recurrence; sterols

The C. glabrata ERG11 gene, encoding the cytochrome P-450-dependent `-14 demethylase, was deleted in order to assess the effect on sterol synthesis, aerobic viability and azole susceptibility. A mutant in which both ERG3 and ERG11 was deleted was aerobically viable and accumulate 14methylfecosterol. A mutant in which only ERG11 was deleted was not aerobically viable but gave rise to an aerobically viable revertant which accumulated both lanosterol and obtusifoliol. This ERG11 mutant had an intact ERG3 gene and increased ERG3 message on Northern analysis. This contrasts with S. cereviseae, in which aerobically viable ERG11 revertants have no functional ERG3 gene. The ERG11 revertant and the ERG3, ERG11 mutant were resistant to azoles, slightly more resistant to amphotericin B and more readily killed by human neutrophils or hydrogen peroxide. We have enrolled four patients in our study of oropharyngeal candidiasis in AIDS patients. One of the four had increased azole resistance in both his C. albicans and C. glabrata isolates at time of relapse. The mechanism by which resistance occurred is under study.

梭glabrata ERG 11基因，编码细胞色素P-450依赖的“-14 删除脱甲基酶，以评估对甾醇的影响 合成、有氧活力和唑敏感性。 的突变体 ERG 3和ERG 11都被删除，是有氧活性的，并积累 14甲基粪甾醇 仅缺失ERG 11的突变体不表达ERG 11。 但产生了一种好氧活回复突变体， 积累羊毛甾醇和钝叶醇。 这个ERG 11突变体有一个 在北方分析上，ERG 3基因完整且ERG 3信息增加。 这 与S。cereviseae，其中有氧活性ERG 11 回复突变体没有功能性ERG 3基因。 ERG 11回复突变体和 ERG 3、ERG 11突变株对唑类药物耐药， 更容易被人中性粒B或氢杀死 过氧化物 我们在口咽念珠菌病的研究中招募了四名患者 在艾滋病患者中。 四个人中有一个在两个人中都增加了唑类药物的耐药性。 他的指挥白色念珠菌和念珠菌。光滑的分离物在复发时。 的 耐药性发生的机制正在研究中。