北京某三级医院耳念珠菌临床分离株:鉴定、抗真菌药物敏感性及基因组特征  

Candida Auris Clinical Isolate from a Tertiary Hospital in Beijing:Identification,Antifungal Susceptibility,and Genomic Characteristics

作　　者：闫琳琳 杨瑞锋 YAN Linlin;YANG Ruifeng(Department of Clinical Laboratory,Peking University Shougang Hospital,Beijing 100144,China)

机构地区：[1]北京大学首钢医院检验科,北京100144

出　　处：《标记免疫分析与临床》2025年第2期374-381,共8页Labeled Immunoassays and Clinical Medicine

基　　金：石景山区医学重点扶持专科建设项目(编号:石卫健医发[2020]21号)。

摘　　要：目的分析北京某三级医院临床分离耳念珠菌的鉴定、抗真菌药物敏感性和基因组特征。方法对临床血培养分离的耳念珠菌进行抗真菌药敏试验、全基因组测序、系统发育分析及SNP分析等。结果耳念珠菌分离株PUSH159对氟康唑耐药,属于南亚分支。在分离株PUSH159中检测到多个耐药相关基因,包括外排泵相关基因MDR1、CDR1、CDR4、SNQ2和ARB1,以及唑类药物靶基因ERG11。致病性分析显示,分离株PUSH159存在多种既往报道的与白色念珠菌相关的毒力因子,但其毒力降低或丧失致病性。SNP分析显示,分离株PUSH159携带多个耐药相关基因突变,包括ERG11热点突变Y132F、CDR1错义突变E709D,SNQ2错义突变K52N和E464K。结论本研究提供了分离株PUSH159对氟康唑耐药和进化支的遗传基础,支持了南亚分支耳念珠菌对氟康唑敏感性的差异,为北京地区出现南亚分支氟康唑耐药耳念珠菌提供了早期预警。Objective To investigate the identification process,antifungal susceptibility,and genomic characteristics of Candida auris isolate in the blood from a tertiary hospital in Beijing.Methods The antifungal susceptibility testing,whole genome sequencing,phylogenetic analysis,and SNP analysis were conducted in this study.Results C.auris isolate PUSH159 was resistant to fluconazole and belongs to South Asian clade.Multiple drug resistance-associated genes were detected in isolate PUSH159,including efflux determinants MDR1,CDR1,CDR4,SNQ2 and ARB1,as well as azole target gene ERG11.Phylogenetic analysis revealed that isolate PUSH159 had multiple previously reported C.albicans-related virulence determinants,but with a decreased virulence or loss of pathogenicity.SNP analysis showed that isolate PUSH159 had several drug resistance-associated gene mutations,including a hot-spot mutation Y132F in the azole target gene ERG11,E709D missense mutation in the CDR1 ABC transporter gene,and K52N and E464K missense mutations in the SNQ2 gene.Conclusion This study provides the genetic knowledge basis of fluconazole resistance and genetic clade of isolate PUSH159,supporting the difference in susceptibility to fluconazole within the South Asian clade,and provides an early warning for the emergence of South Asian clade fluconazole-resistant C.auris in Beijing.

关 键 词：耳念珠菌 真菌血症 氟康唑耐药 南亚分支 

分 类 号：R378[医药卫生—病原生物学]