耐唑类抗真菌药白念珠菌标准菌株的建立与评价  

Establishment and evaluation of standard strains of azole antifungal drug-resistant Candida albicans

作　　者：魏销玥 张舒 耿圆圆 张慧芳[1] 肖迪[1] 张建中[1] 龚杰 Wei Xiaoyue;Zhang Shu;Geng Yuanyuan;Zhang Huifang;Xiao Di;Zhang Jianzhong;Gong Jie(State Key Laboratory for Infectious Disease Prevention and Control,National Institute for Communicable Disease Control and Prevention,Chinese Center for Disease Control and Prevention,Beijing 102206,China)

机构地区：[1]中国疾病预防控制中心传染病预防控制所,传染病国家重点实验室,北京102206

出　　处：《疾病监测》2023年第12期1473-1477,共5页Disease Surveillance

基　　金：国家重点研发计划项目(No.2022YFC2504800);中国疾病预防控制中心传染病预防控制所自主课题(No.TS202307);公共卫生应急反应机制的运行–传染病防控(No.102393220020020000029)。

摘　　要：目的建立耐唑类抗真菌药的白念珠菌(C.albicans)标准菌株,参照《病原微生物菌(毒)种国家标准株评价技术标准》(WS/T 812—2022)要求做好病原微生物菌(毒)种保藏工作,为其他真菌标准菌株的候选提供参考方法。方法通过菌株表型、鉴定、测试9种抗真菌药物敏感性和耐药基因,评估菌株保存状态下的表型稳定性和活性。结果菌株经内部转录间隔区(ITS)序列分析和质谱仪(MALDI-TOF MS)鉴定为白念珠菌,连续传代十次仍有稳定的分子生物学特征。该菌株对氟康唑、伏立康唑、伊曲康唑、泊沙康唑的最低抑菌浓度(MIC)分别为16 mg/L、0.5 mg/L、0.5 mg/L和0.5 mg/L,耐药性与ERG11基因双点突变(A114S、Y257H)及编码药物外排泵基因突变(A736V)相关。菌株在–80℃表型稳定至少6个月。结论本研究建立了耐唑类抗真菌药白念珠菌标准菌株,为白念珠菌感染性疾病的综合防治提供了重要的研究对象和物质基础,对于国家生物安全具有重要的战略意义。Objective Establishing a standard strain of Candida albicans(C.albicans),a resistant azole antifungal drug,and conducting the preservation work of pathogenic microbial strains according to the Technical Requirements for Evaluation of National Standard Strains of Pathogenic Microorganisms(WS/T 812—2022),will provide a standardized reference method for other fungal standard strains in the future.Methods Assess the phenotypic stability and activity of strain preservation through phenotypic characterization,identification,and testing of sensitivity to nine antifungal drugs and resistance genes.Results Through internal transcribed spacer(ITS)sequence analysis and Matrix assisted laser desorption/ionization-Time of flight mass spectrometry(MALDI-TOF MS),the strain was confirmed to be C.albicans.The strain maintained stable molecular characteristics following ten sequential passages.The minimum inhibitory concentrations(MICs)of the strain to fluconazole,voriconazole,itraconazole,and posaconazole were 16 mg/L,0.5 mg/L,0.5 mg/L,and 0.5 mg/L,respectively.Its resistance was associated with mutations in the ERG11 gene(A114S,Y257H)and the drug efflux pump-encoding gene(A736V).The strain could be stably preserved at–80℃for at least 6 months.Conclusion This study established a standardized strain of Candida albicans for antifungal drugs in the azole class,providing a crucial research subject and material foundation for the comprehensive prevention and treatment of Candida albicans infectious diseases.This carries significant strategic importance for national biosecurity.

关 键 词：白念珠菌 标准菌株 唑类抗真菌药物 耐药性 

分 类 号：R211[医药卫生—中医学] R37[生物学—微生物学] Q939.99