11例肾移植术后合并隐球菌病患者的新生隐球菌菌株遗传多样性研究

中国真菌学杂志　 2020, Vol. 15 　Issue (6): 338-343.

11例肾移植术后合并隐球菌病患者的新生隐球菌菌株遗传多样性研究

朱信霖^1,2, 洪南³, 张超^1,2, 潘炜华^1,2, 蔡良奇⁴, 李小静⁵, 陈敏^1,2, 廖万清^1,2

1. 海军军医大学长征医院皮肤科, 上海 200003;
2. 上海市医学真菌分子生物学重点实验室, 上海 200003;
3. 金陵医院皮肤科, 南京 210002;
4. 厦门大学附属第一医院皮肤科, 厦门 361000;
5. 河北工程大学附属医院皮肤科, 邯郸 056000

收稿日期:2020-07-09 发布日期:2020-12-28
通讯作者: 廖万清,E-mail:liaowanqing@smmu.edu.cn;陈敏,E-mail:chenmin@smmu.edu.cn E-mail:liaowanqing@smmu.edu.cn;chenmin@smmu.edu.cn
作者简介:朱信霖,男(汉族),硕士研究生在读.E-mail:6299397@qq.com
基金资助:
国家自然科学基金重点国际（地区）合作研究项目（81720108026）；国家科技重大专项（2018ZX10101003）；上海市科委（2017ZZ01024-001）

Genotypic diversity of 11 Cryptococcus neoformans isolates from kidney transplantation patients with cryptococcosis

ZHU Xin-lin^1,2, HONG Nan³, ZHANG Chao^1,2, PAN Wei-hua^1,2, CAI Liang-qi⁴, LI Xiao-jing⁵, CHEN Min^1,2, LIAO Wan-qing^1,2

1. Department of Dermatology, Changzheng Hospital, Naval Military Medical University, Shanghai 200003, China;
2. Shanghai Key Laboratory of Molecular Medical Mycology, Shanghai 200003, China;
3. Department of Dermatology, Jinling Hospital, Nanjing, 210002, China;
4. Department of Dermatology, the First Affiliated Hospital of Xiamen University, Xiamen 361000, China;
5. Department of Dermatology, Affiliated Hospital of Hebei Engineering University, Handan 056000, China

Received:2020-07-09 Published:2020-12-28

摘要/Abstract

摘要： 目的分析11例肾移植术后并发隐球菌病患者的新生隐球菌株的基因型分布等遗传多样性特征，为提高肾移植术后患者并发隐球菌病的诊治水平提供科学基础。方法采用国际人与动物真菌病学会（International Society for Human and Animal Mycology，ISHAM）推荐的多位点序列分型（multi locus sequence typing，MLST）方法对分离自我院9例及外院2例肾移植术后患者的11株新生隐球菌进行分子分型及系统发育分析，并与22株分离自免疫功能正常的隐球菌病患者的菌株进行群体多样性特征比较。结果本研究纳入的11株新生隐球菌均为VNⅠ基因型菌株（交配型均为MAT α型），其中包含5种ST分子型，且以ST5型菌株为主（46%，5/11）。系统发育分析结果与主成分分析（principal component analysis，PCA）结果均显示来自肾移植患者的ST5型菌株与来自免疫功能正常患者的ST5型菌株汇聚在一个类群。分离自肾移植术后隐球菌病患者的菌株群体（π=0.00150）的核酸多样性（π）高于分离自免疫功能正常患者的菌株群体（π=0.00088），且分离自肾移植术后患者的ST5型菌株占比较分离自免疫功能正常的隐球菌病患者的ST5型菌株低（P=0.033）。结论该11例肾移植术后并发隐球菌病患者的致病菌株遗传多样性显著高于分离自免疫功能正常的菌株，可能与不同ST型新生隐球菌菌株的毒力不同及肾移植术后患者的免疫功能处于抑制状态有关，本研究为后续的肾移植术后患者并发隐球菌病的精准治疗提供了科学基础。

关键词: 新生隐球菌, 分子分型, 系统发育, 肾移植

Abstract: Objective To analyze genotypic diversity of 11 clinical isolates of Cryptococcus neoformans from kidney transplantation patients with cryptococcosis, which could lay the foundation for precisely therapeutic strategies on cryptococcosis associated with kidney transplantation. Methods A total of 11 C. neoformans isolates were genotyped using the Multi locus sequence typing (MLST) consensus scheme, which was recommended by the International Society for Human and Animal Mycology (ISHAM). The differences of population diversity characteristics were compared between our isolates and 22 isolates collected from 22 cryptococcosis patients with immunocompetent status. Results With the predominant ST5 (46%, 5/11), all 11 Cryptococcal isolates in this study were identified as VNⅠ molecular type (MATα type), including 5 ST types. Both results of phylogenetics and principal component analysis (PCA) showed that ST5 isolates from cryptococcosis with kidney transplant and immunocompetent status were identical. The nucleotide diversity (π) of the isolates from cryptococcosis with kidney transplant was significantly higher than that fromimmunocompetent patients. And the proportion of ST5 isolates collected from kidney transplant patients was significantly lower than that from immunocompetent patients (P=0.033). Conclusion The genetic diversity of C. neoformans isolates from cryptococcosis with kidney transplantation are significantly higher than that from cryptococcosis patients with immunocompetent status. It may be related to different STs of C. neoformans isolates with different virulence and the suppressed immunological function in patients with kidney transplantation. A more precise treatment strategies is needed in cryptococcosis patients with kidney transplantation.

Key words: Cryptococcus neoformans, genotype, phylogenetic, kidney transplant

中图分类号:

R379.5

朱信霖, 洪南, 张超, 潘炜华, 蔡良奇, 李小静, 陈敏, 廖万清. 11例肾移植术后合并隐球菌病患者的新生隐球菌菌株遗传多样性研究[J]. 中国真菌学杂志, 2020, 15(6): 338-343.

ZHU Xin-lin, HONG Nan, ZHANG Chao, PAN Wei-hua, CAI Liang-qi, LI Xiao-jing, CHEN Min, LIAO Wan-qing. Genotypic diversity of 11 Cryptococcus neoformans isolates from kidney transplantation patients with cryptococcosis[J]. Chinese Journal of Mycology, 2020, 15(6): 338-343.

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