转录因子Pho4参与白念珠菌药物敏感性的调控

发布时间：2018-01-21 21:50

本文关键词： 白念珠菌转录因子药物敏感性药物外排　出处：《中国真菌学杂志》2016年02期 　论文类型：期刊论文

【摘要】：目的通过对缺失相应转录因子基因的白念珠菌进行抗真菌药物敏感性的筛选,考察转录因子对白念珠菌耐药性的影响及调控机制。方法通过微量液基稀释法、点板实验(Spot Assay)检测实验菌株对抗真菌药物的敏感性。采用实时定量PCR(RT-PCR)的方法检测白念珠菌耐药性相关MDR1,CDR1以及ERG11的表达,并通过检测菌株对罗丹明6G的外排能力进一步检测菌株对抗真菌药物的外排能力。结果最低抑菌浓度(minimal inhibitory concentration,MIC)测定和Spot Assay实验结果表明,与亲本菌相比,PHO4基因缺失菌对氟康唑、咪康唑的敏感性显著升高。虽然耐药相关基因的表达增加,但对罗丹明6G的外排能力降低,抗氧化应激能力下降。结论转录因子Pho4的缺失可能通过降低白念珠菌的抗氧化应激能力,减弱对药物的外排作用而导致对唑类药物敏感,但其具体的调控机制有待进一步研究。
[Abstract]:Objective to investigate the effect of transcription factor on resistance of Candida albicans and its regulatory mechanism by screening the antimicrobial susceptibility of Candida albicans with the deletion of the corresponding transcription factor gene. Methods microamounts of liquid based dilution were used to detect the drug resistance of Candida albicans. Spot assay was used to detect the susceptibility of the experimental strains to antifungal drugs, and real-time quantitative PCR RT-PCR was used to detect the drug-resistance related MDR1 of Candida albicans. Expression of CDR1 and ERG11. The efflux ability of the strain to Rhodamine 6G was further determined by the detection of the efflux ability of the strain against fungal drugs. Minimal inhibitory concentration. The results of MICM and Spot Assay test showed that compared with the parent strain, the PHO4 gene deletion bacteria was resistant to fluconazole. The sensitivity of miconazole was significantly increased. Although the expression of drug-resistance-related genes increased, the efflux ability of Rhodamine 6G was decreased. Conclusion the absence of transcription factor Pho4 may lead to the sensitivity of Pho4 by reducing the antioxidant stress ability of Candida albicans and the efflux of drugs. But its specific regulation mechanism needs further research.
【作者单位】：中国人民解放军第二军医大学药学院新药研究中心;
【基金】：国家自然科学基金(812735560) 国家重点基础研究973计划(2013CB531600)
【分类号】：R379.4
【正文快照】： [Chin J Mycol,2016,11(2):65-69]白念珠菌作为一种条件致病真菌,在正常人体内可以长期、无害地共生,并与其他菌群保持平衡,机体自身的免疫力足以抵御白念珠菌的侵袭。当机体免疫力下降时,对白念珠菌的抵抗能力随之下降,引发从皮肤黏膜表层到危及生命的系统性真菌感染。近年来

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