转录因子Cup2对白念珠菌铜离子代谢、氧化应激调控作用的初步研究

目的 利用白念珠菌（Candida albicans）不同转录因子基因缺失菌,考察参与调控铜离子（Cu2＋）代谢和氧化应激的重要转录因子.方法 点板实验（spot assay）、生长曲线法.结果 spot assay筛选发现,转录因子Cup2缺失菌Cup2Δ/Δ对Cu2＋的敏感性增加,进一步研究表明Cup2Δ/Δ在含5 mmol/L的Cu2＋培养液中生长缓慢;Cup2Δ/Δ对H2O2的敏感性也有所增加,而且Cu2＋协同H2O2发挥抑菌作用,在BCS螯合Cu2＋后,增加了Cup2Δ/Δ和亲本菌SN250对H2O2诱导的氧化应激的耐受性.在氟康唑、咪康唑和酮康唑敏感性实验中,Cup2Δ/Δ并未表现...

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Bibliographic Details
Published in药学实践杂志 Vol. 35; no. 3; pp. 224 - 228
Main Author 张金宇 王丽红 秦玉璘 张璐璐 姜远英 曹永兵
Format Journal Article
LanguageChinese
Published 第二军医大学药学院新药研究中心,上海,200433%中国药科大学,江苏南京,211198 2017
Subjects
白念珠菌
药物敏感性
转录因子Cup2
过氧化氢
铜离子（Cu2＋）
铜离子(Cu2+)
过氧化氢
药物敏感性
Candida albicans
白念珠菌
drug susceptibility
transcription factor Cup2
copper ion (Cu,2+)
转录因子Cup2
hydrogen peroxide(H2O2)
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ISSN1006-0111
DOI10.3969/j.issn.1006-0111.2017.03.008

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Summary:目的 利用白念珠菌（Candida albicans）不同转录因子基因缺失菌,考察参与调控铜离子（Cu2＋）代谢和氧化应激的重要转录因子.方法 点板实验（spot assay）、生长曲线法.结果 spot assay筛选发现,转录因子Cup2缺失菌Cup2Δ/Δ对Cu2＋的敏感性增加,进一步研究表明Cup2Δ/Δ在含5 mmol/L的Cu2＋培养液中生长缓慢;Cup2Δ/Δ对H2O2的敏感性也有所增加,而且Cu2＋协同H2O2发挥抑菌作用,在BCS螯合Cu2＋后,增加了Cup2Δ/Δ和亲本菌SN250对H2O2诱导的氧化应激的耐受性.在氟康唑、咪康唑和酮康唑敏感性实验中,Cup2Δ/Δ并未表现出对唑类药物敏感.结论 敲除转录因子Cup2,可增加白念珠菌对Cu2＋和H2O2的敏感性.转录因子Cup2可能参与调控白念珠菌对Cu2＋的代谢和H2O2诱导的氧化应激反应,但并未参与对唑类药物耐药性的调控.
Bibliography:31-1685/R
Objective To detect the transcription factors of copper ion （Cu,2＋） metabolism and oxidative stress by Candida albicans knocked down different transcription factors.Methods Spot assay, growth curve were used.Results The sensitivity to Cu,2＋ in Cup2Δ/Δ was increasing and the growth of Cup2Δ/Δ was inhibited in 5 mmol /L Cu,2＋ medium.The results showed that Cup2Δ/Δ also increased the sensitivity to H2O2, interestingly, Cu,2＋and H2O2 played a synergistic antifungal effect.The tolerance of Cup2Δ/Δ and SN250 to H2O2 induced oxidative stress was increased after BCS chelating Cu,2＋.In the fluconazole, miconazole and ketoconazole susceptibility experiments, Cup2Δ/Δ did not show susceptibility to azole drugs.Conclusion Knockout transcription factor Cup2, which could increase the sensitivity to Cu,2＋ and H2O2in Candida albicans.Transcription factor Cup2 might be involved in the regulation and control of Candida albicansmetabolism on Cu,2＋ and oxidative stress induced by H2O2, but not involved in the regulation
ISSN:1006-0111
DOI:10.3969/j.issn.1006-0111.2017.03.008