外阴阴道念珠菌病白念珠菌交配型基因分析及其致病性研究  

Mating-Type Locus and virulence in Candida albicans from vulvovaginal candidiasis

作　　者：单莹莹[1] 李健玲[1] 黎婷[1] 刘小平[2] 樊尚荣[1,3] 

机构地区：[1]北京大学深圳医院妇产科,深圳518036 [2]北京大学深圳医院检验科,深圳518036 [3]深圳市科创委妇科疾病重点实验室,深圳518036

出　　处：《现代妇产科进展》2015年第7期481-486,共6页Progress in Obstetrics and Gynecology

基　　金：深圳科创委基础研究项目(No:201201001和JCYJ20140415162338813)

摘　　要：目的：研究临床致病白念珠菌交配型基因MTL纯合子与杂合子的流行病学特点,分析其与外阴阴道念珠菌病患者的临床特征、白念珠菌致病力及毒力的关系。方法：通过普通PCR对临床外阴阴道念珠菌病患者阴道分泌物分离的致病白念珠菌MTL基因进行检测,应用实时荧光定量PCR反应分析MTL纯合子与杂合子中毒力相关基因ASL3、SAP1和HWP1基因的表达,并采用Rosco药片扩散法对白念珠菌进行体外药物敏感试验。结果：1338株白念珠菌中,1330株为MTLa/α杂合子,8株为MTL纯合子（7株MTLa/a纯合子,1株MTLα/α纯合子）。8株MTL纯合子所致外阴阴道念珠菌病患者中6例患者达到真菌学治愈。与杂合子相比,白念珠菌MTL纯合子对唑类药物耐药性较高（0~75%vs 0~2.7%,P〈0.05）。毒力相关基因ASL3在两者中的表达无明显统计学差异,SAP1在MTL杂合子中表达稍高（1.02±0.68 vs 0.83±0.31,P〉0.05）,而HWP1在杂合子中表达明显增高（1.71±1.42 vs 1.20±0.62,P〈0.05）。结论：外阴阴道念珠菌病白念珠菌MTL纯合子在外阴阴道念珠菌病患者中流行率较低;与杂合子相比,MTL纯合子耐药性增加;而毒力相关基因HWP1、SAP1和ASL3在纯合子中表达降低,这与其临床特征相符。Objective：To analyse the epidemiological characteristics of MTL locus het- erozygous isolates and MTL locus homozygous isolates, and the relationship between the MTL lo- cus and clinical characteristics of vulvovaginal candidiasis （VVC） patients, pathogenicity or virulence of Candida albicans. Methods：The PCR was used to detect the MTL genes in Candi- da albieans, which were isolated from vaginal secretions of VVC patients. Real-time fluorescent quantitative PCR reaction was applicated to analyze the expression of virulence factors HWP1 SAPI and ASL3. Drug sensitivity tests in vitro were also performed by Rosco tablets diffusion method. Result：We detected 1338 Candida albicans isolates and found 1330 MTL locus hetero- zygous isolates and 8 were MTL locus homozygous isolates, of which 7 isolates were MTLa/a and one isolate was MTIα/α. Six of eight patients with VVC caused by C albicans MTL locus homo- zygous isolates were cured. The azoles resistant rates of homozygous isolates were higher than those of heterozygous isolates （0 - 75% vs 0 - 2.7% ,P〈0.05 ）. Expression levels of virulence- related genes ASL3 were similar in heterozygous isolates and in homozygous isolates （0.35 ±0.32 vs 0.27±0.25 ,P〉O. 05 ） ;SAP1 were a little higher in heterozygous isolates than in homo- zygous isolates （ 1.02±0.68 vs 0.83±0.31 ,P〉0.05 ） ;HWP1 were significantly higher in het- erozygous isolates than in homozygous isolates （ 1.71 ±1,42 vs 1.20±0.62 ,P〈0.05 ）. Conclu- sions：The MTL locus homozygous isolates were infrequent in patients infected with Candida al- bicans ; antifungal resistant rates were higher in MTL locus homozygous isolates than in heterozy- gous isolates ; the expression of virulence factors HWP1, SAP1 and ASL3 in mating-type locus homozygosis isolates were lower than those in heterozygous isolates,which was compatible with their clinical characteristics.

关 键 词：外阴阴道念珠菌病 白念珠菌 交配型基因 ASL3 HWP1 ASP1 

分 类 号：R711.73[医药卫生—妇产科学]