Ploidy Variation and Spontaneous Haploid-Diploid Switching of Candida glabrata Clinical Isolates

ABSTRACT The human fungal pathogen Candida glabrata is phylogenetically closely related to Saccharomyces cerevisiae, a model eukaryotic organism. Unlike S. cerevisiae, which has both haploid and diploid forms and a complete sexual cycle, C. glabrata has long been considered a haploid and asexual spe...

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Main Authors: Qiushi Zheng, Jing Liu, Juanxiu Qin, Bingjie Wang, Jian Bing, Han Du, Min Li, Fangyou Yu, Guanghua Huang
Format: Article
Language:English
Published: American Society for Microbiology 2022-08-01
Series:mSphere
Subjects:
Online Access:https://journals.asm.org/doi/10.1128/msphere.00260-22
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author Qiushi Zheng
Jing Liu
Juanxiu Qin
Bingjie Wang
Jian Bing
Han Du
Min Li
Fangyou Yu
Guanghua Huang
author_facet Qiushi Zheng
Jing Liu
Juanxiu Qin
Bingjie Wang
Jian Bing
Han Du
Min Li
Fangyou Yu
Guanghua Huang
author_sort Qiushi Zheng
collection DOAJ
description ABSTRACT The human fungal pathogen Candida glabrata is phylogenetically closely related to Saccharomyces cerevisiae, a model eukaryotic organism. Unlike S. cerevisiae, which has both haploid and diploid forms and a complete sexual cycle, C. glabrata has long been considered a haploid and asexual species. In this study, we analyzed the ploidy states of 500 clinical isolates of C. glabrata from four Chinese hospitals and found that approximately 4% of the isolates were in or able to spontaneously switch to an aneuploid (genomic DNA, 1N-2N), diploid (2N), or hyperdiploid (>2N) form under in vivo or in vitro conditions. Stable diploid cells were identified in 3% of the isolates (15/500). Of particular interest, one clinical strain existed only in the diploid form. Multilocus sequence typing (MLST) assays revealed two major genetic clusters (A and B) of C. glabrata isolates. Most of the isolates (70%) from China belonged to the A cluster, whereas most of the isolates from other countries (such as Iran, Japan, United States, and European countries) belonged to the B cluster. Further investigation indicated that C. glabrata cells of different ploidy forms differed in a number of respects, including morphologies, antifungal susceptibility, virulence, and global gene expression profiles. Additionally, C. glabrata could undergo spontaneous switching between the diploid and haploid forms under both in vitro and in vivo conditions. Given the absence of an apparent sexual phase, one would expect that the ploidy shifts could function as an alternative strategy that promotes genetic diversity and benefits the ability of the fungus to rapidly adapt to the changing environment. IMPORTANCE The human fungal pathogen Candida glabrata has long been thought to be a haploid organism. Here, we report the population structure and ploidy states of 500 clinical isolates of C. glabrata from China. To our surprise, we found that the ploidy of a subset of clinical isolates varied dramatically. Some isolates were in or able to switch to an aneuploid, diploid, or hyperdiploid form. C. glabrata cells with different ploidy differed in a number of biological respects, including morphology, antifungal susceptibility, virulence, and global gene expression profile. Given the absence of an apparent sexual phase in this fungus, we propose that ploidy switching could be a strategy for rapid adaptation to environmental changes and could function as an alternative to sexual reproduction.
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spelling doaj.art-fbb92342271b49e0ab69593aed916a592022-12-22T03:44:54ZengAmerican Society for MicrobiologymSphere2379-50422022-08-017410.1128/msphere.00260-22Ploidy Variation and Spontaneous Haploid-Diploid Switching of Candida glabrata Clinical IsolatesQiushi Zheng0Jing Liu1Juanxiu Qin2Bingjie Wang3Jian Bing4Han Du5Min Li6Fangyou Yu7Guanghua Huang8Shanghai Institute of Infectious Disease and Biosecurity, Department of Infectious Diseases, Huashan Hospital and State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, ChinaShanghai Institute of Infectious Disease and Biosecurity, Department of Infectious Diseases, Huashan Hospital and State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, ChinaDepartment of Laboratory Medicine, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Clinical Laboratory, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, ChinaShanghai Institute of Infectious Disease and Biosecurity, Department of Infectious Diseases, Huashan Hospital and State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, ChinaShanghai Institute of Infectious Disease and Biosecurity, Department of Infectious Diseases, Huashan Hospital and State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, ChinaDepartment of Laboratory Medicine, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Clinical Laboratory, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, ChinaShanghai Institute of Infectious Disease and Biosecurity, Department of Infectious Diseases, Huashan Hospital and State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, ChinaABSTRACT The human fungal pathogen Candida glabrata is phylogenetically closely related to Saccharomyces cerevisiae, a model eukaryotic organism. Unlike S. cerevisiae, which has both haploid and diploid forms and a complete sexual cycle, C. glabrata has long been considered a haploid and asexual species. In this study, we analyzed the ploidy states of 500 clinical isolates of C. glabrata from four Chinese hospitals and found that approximately 4% of the isolates were in or able to spontaneously switch to an aneuploid (genomic DNA, 1N-2N), diploid (2N), or hyperdiploid (>2N) form under in vivo or in vitro conditions. Stable diploid cells were identified in 3% of the isolates (15/500). Of particular interest, one clinical strain existed only in the diploid form. Multilocus sequence typing (MLST) assays revealed two major genetic clusters (A and B) of C. glabrata isolates. Most of the isolates (70%) from China belonged to the A cluster, whereas most of the isolates from other countries (such as Iran, Japan, United States, and European countries) belonged to the B cluster. Further investigation indicated that C. glabrata cells of different ploidy forms differed in a number of respects, including morphologies, antifungal susceptibility, virulence, and global gene expression profiles. Additionally, C. glabrata could undergo spontaneous switching between the diploid and haploid forms under both in vitro and in vivo conditions. Given the absence of an apparent sexual phase, one would expect that the ploidy shifts could function as an alternative strategy that promotes genetic diversity and benefits the ability of the fungus to rapidly adapt to the changing environment. IMPORTANCE The human fungal pathogen Candida glabrata has long been thought to be a haploid organism. Here, we report the population structure and ploidy states of 500 clinical isolates of C. glabrata from China. To our surprise, we found that the ploidy of a subset of clinical isolates varied dramatically. Some isolates were in or able to switch to an aneuploid, diploid, or hyperdiploid form. C. glabrata cells with different ploidy differed in a number of biological respects, including morphology, antifungal susceptibility, virulence, and global gene expression profile. Given the absence of an apparent sexual phase in this fungus, we propose that ploidy switching could be a strategy for rapid adaptation to environmental changes and could function as an alternative to sexual reproduction.https://journals.asm.org/doi/10.1128/msphere.00260-22diploidyploidy changeadaptationCandida glabrataclinical isolateshaploidy
spellingShingle Qiushi Zheng
Jing Liu
Juanxiu Qin
Bingjie Wang
Jian Bing
Han Du
Min Li
Fangyou Yu
Guanghua Huang
Ploidy Variation and Spontaneous Haploid-Diploid Switching of Candida glabrata Clinical Isolates
mSphere
diploidy
ploidy change
adaptation
Candida glabrata
clinical isolates
haploidy
title Ploidy Variation and Spontaneous Haploid-Diploid Switching of Candida glabrata Clinical Isolates
title_full Ploidy Variation and Spontaneous Haploid-Diploid Switching of Candida glabrata Clinical Isolates
title_fullStr Ploidy Variation and Spontaneous Haploid-Diploid Switching of Candida glabrata Clinical Isolates
title_full_unstemmed Ploidy Variation and Spontaneous Haploid-Diploid Switching of Candida glabrata Clinical Isolates
title_short Ploidy Variation and Spontaneous Haploid-Diploid Switching of Candida glabrata Clinical Isolates
title_sort ploidy variation and spontaneous haploid diploid switching of candida glabrata clinical isolates
topic diploidy
ploidy change
adaptation
Candida glabrata
clinical isolates
haploidy
url https://journals.asm.org/doi/10.1128/msphere.00260-22
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