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SDH2基因在白念珠菌环境适应性中的作用

来源：花匠小妙招时间：2024-11-02 22:57

SDH2基因在白念珠菌环境适应性中的作用投稿时间：2022-01-26 修订日期：2022-06-23 点此下载全文引用本文：王欣荣,鲁仁义,王彦.SDH2基因在白念珠菌环境适应性中的作用[J].药学实践杂志,2022,40(4):309~313 摘要点击次数: 697 全文下载次数: 863 作者单位E-mail王欣荣海军军医大学药学系军特药研究中心, 上海 200433 鲁仁义海军军医大学药学系军特药研究中心, 上海 200433 王彦海军军医大学药学系军特药研究中心, 上海 200433 wangyansmmu@126.com 基金项目:军队生物安全研究专项（20SWAQX29-1-6）中文摘要:目的探究SDH2基因在白念珠菌环境适应性中的作用。方法以野生型白念珠菌SC5314、SDH2基因敲除菌sdh2Δ/Δ、基因回复菌sdh2Δ/SDH2为实验对象；应用点板实验考察野生型菌、SDH2缺失菌和回复菌对外界压力刺激剂和抗真菌药物的敏感性；采用罗丹明6G外排实验考察SDH2基因缺失对白念珠菌药物外排能力的影响。结果 SDH2基因缺失后白念珠菌对细胞壁应激刺激剂咖啡因、氧化应激刺激剂二酰胺和甲萘醌表现出轻微耐受，值得注意的是SDH2基因敲除菌sdh2Δ/Δ对唑类抗真菌药物的敏感性明显增高，SDH2缺失导致白念珠菌药物外排能力下降。结论 SDH2缺失会导致白念珠菌对环境适应性的改变，包括对外界环境压力应答的改变和对唑类抗真菌药物敏感性的增加，以SDH2为靶基因，开发真菌特异性SDH2抑制剂，有望发现与唑类药物协同的新型抗真菌药物。中文关键词:白念珠菌 SDH2 环境适应性压力应激药物敏感性 The role of SDH2 gene in the environmental adaptability of Candida albicans Abstract:Objective To investigate the role of SDH2 gene in the environmental adaptability of Candida albicans. Methods Wild-type C. albicans strain SC5314, SDH2 gene knockout mutant sdh2Δ/Δ and reintegrated strain sdh2Δ/SDH2 were used as experimental objects. Spot assay was conducted to assess the sensitivity of the WT C. albicans strain SC5314, SDH2 gene knockout mutant sdh2Δ/Δ and reintegrated strain sdh2Δ/SDH2 to external stress stimulants and antifungal drugs. The effect of SDH2 gene deletion on drug efflux ability of C. albicans was determined by rhodamine 6G efflux assay. Results After SDH2 gene deletion, C. albicans showed slight tolerance to cell wall stress stimulants caffeine, oxidative stress stimulators diamide and menadione. Notably, the sensitivity of SDH2 gene knockout mutant sdh2Δ/Δ to azole antifungal drugs was significantly increased. The drug efflux capacity of C. albicans was decreased due to the deletion of SDH2 gene. Conclusion SDH2 gene deletion lead to changes in environmental adaptability of C. albicans, including changes in response to external environmental stress and increased sensitivity to azole antifungal drugs. The development of fungal-specific inhibitor targeting SDH2 gene may lead to the discovery of new antifungal drugs which have synergistic effect with azole drugs.keywords:Candida albicans SDH2 environmental adaptability stress response drug sensitivity 查看全文查看/发表评论下载PDF阅读器关闭参考文献(共9条):[1] PFALLER M A, DIEKEMA D J. Epidemiology of invasive mycoses in North America[J]. Crit Rev Microbiol,2010,36(1):1-53[2] ENOCH D A, YANG H N, ALIYU S H, et al. The changing epidemiology of invasive fungal infections[J]. Methods Mol Biol,2017,1508:17-65[3] BROWN G D, DENNING D W, GOW N A, et al. Hidden killers: human fungal infections[J]. Sci Transl Med,2012,4(165):165rv13[4] ENE I V, ADYA A K, WEHMEIER S, et al. Host carbon sources modulate cell wall architecture, drug resistance and virulence in a fungal pathogen[J]. Cell Microbiol,2012,14(9):1319-1335[5] SUN N, FONZI W, CHEN H, et al. Azole susceptibility and transcriptome profiling in Candida albicans mitochondrial electron transport chain complex I mutants[J]. Antimicrob Agents Chemother,2013,57(1):532-542[6] THOMAS E, ROMAN E, CLAYPOOL S, et al. Mitochondria influence CDR1 efflux pump activity, Hog1-mediated oxidative stress pathway, iron homeostasis, and ergosterol levels in Candida albicans[J]. Antimicrob Agents Chemother,2013,57(11):5580-5599[7] BI S, LV Q Z, WANG T T, et al. SDH2 is involved in proper hypha formation and virulence in Candida albicans[J]. Future Microbiol,2018,13:1141-1156[8] OYEDOTUN K S, LEMIRE B D. The quaternary structure of the Saccharomyces cerevisiae succinate dehydrogenase. Homology modeling, cofactor docking, and molecular dynamics simulation studies[J]. J Biol Chem,2004,279(10):9424-9431[9] HANS S, FATIMA Z, HAMEED S. Insights into the modulatory effect of magnesium on efflux mechanisms of Candida albicans reveal inhibition of ATP binding cassette multidrug transporters and dysfunctional mitochondria[J]. 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