Virulence profiling of Cryptococcus gattii isolates in China: insights from a multi-center study

ABSTRACT Cryptococcus gattii (C. gattii) is emerging as a life-threatening fungus worldwide. However, few data were available in China. In this study, 27 isolates and 32 patient information were collected from several hospitals in China, together with previously reported data (80 cases), to describe...

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Main Authors: Xuelei Zang, Weixin Ke, Yemei Huang, Chen Yang, Jialin Song, Hengyu Deng, Meng Zhou, Qiqi Wang, Yangyu Zhou, Bin Dai, Jin Qian, Dingxia Shen, Linqi Wang, Xinying Xue
Format: Article
Language:English
Published: American Society for Microbiology 2023-12-01
Series:Microbiology Spectrum
Subjects:
Online Access:https://journals.asm.org/doi/10.1128/spectrum.02443-23
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author Xuelei Zang
Weixin Ke
Yemei Huang
Chen Yang
Jialin Song
Hengyu Deng
Meng Zhou
Qiqi Wang
Yangyu Zhou
Bin Dai
Jin Qian
Dingxia Shen
Linqi Wang
Xinying Xue
author_facet Xuelei Zang
Weixin Ke
Yemei Huang
Chen Yang
Jialin Song
Hengyu Deng
Meng Zhou
Qiqi Wang
Yangyu Zhou
Bin Dai
Jin Qian
Dingxia Shen
Linqi Wang
Xinying Xue
author_sort Xuelei Zang
collection DOAJ
description ABSTRACT Cryptococcus gattii (C. gattii) is emerging as a life-threatening fungus worldwide. However, few data were available in China. In this study, 27 isolates and 32 patient information were collected from several hospitals in China, together with previously reported data (80 cases), to describe the geographic distribution of C. gattii. Molecular identification and genetic diversity analysis of the isolates were conducted using multilocus sequence typing, while the microbiological and virulence characteristics were explored through in vitro phenotypic tests and in vivo animal experiments. The findings revealed that patients infected with C. gattii were mainly immunocompetent males, with most showing symptoms of central nervous system involvement. Isolated strains were predominantly distributed in tropical and subtropical regions, with VGI genotype predominance. These strains exhibited marked genetic diversity, identifying 25 distinct sequence types (STs) among the 57 isolates (available data), including three novel STs (ST565, ST567, and ST568). In vitro assays unveiled significant differences between VGI and VGII in growth capacity at 39°C, capsule diameter, melanin production, UV resistance, and antioxidative capacity, with VGII displaying greater resilience. Integrating animal experiments and clinical prognosis showed that pathogenicity did not directly correlate with in vitro virulence phenotypes or molecular genotypes, underscoring virulence’s complexity. Furthermore, histopathological analysis suggested that lung tissue damage might primarily contribute to mouse mortality, particularly with more pathogenic strains causing extensive lung tissue damage. Our study has the potential to provide valuable data for a comprehensive understanding of the microbiological characteristics of C. gattii in China. IMPORTANCE Our study indicates that the molecular typing of Cryptococcus gattii is unrelated to virulence. The integration of animal experiments and clinical prognosis demonstrated that pathogenicity did not exhibit a direct correlation with in vitro virulence phenotypes or molecular genotypes, emphasizing the intricate nature of virulence. In conclusion, our research holds the potential to provide valuable insights into understanding the microbiological attributes of C. gattii in China.
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spelling doaj.art-56d2388df51e481386d48fac343f5e802023-12-12T13:17:19ZengAmerican Society for MicrobiologyMicrobiology Spectrum2165-04972023-12-0111610.1128/spectrum.02443-23Virulence profiling of Cryptococcus gattii isolates in China: insights from a multi-center studyXuelei Zang0Weixin Ke1Yemei Huang2Chen Yang3Jialin Song4Hengyu Deng5Meng Zhou6Qiqi Wang7Yangyu Zhou8Bin Dai9Jin Qian10Dingxia Shen11Linqi Wang12Xinying Xue13Department of Respiratory and Critical Care, Emergency and Critical Care Medical Center, Beijing Shijitan Hospital, Capital Medical University , Beijing, ChinaState Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences , Beijing, ChinaDepartment of Respiratory and Critical Care, Emergency and Critical Care Medical Center, Beijing Shijitan Hospital, Capital Medical University , Beijing, ChinaMedical School of Chinese PLA , Beijing, ChinaWeifang Medical University , Weifang, ChinaWeifang Medical University , Weifang, ChinaSchool of Medical Imaging, Binzhou Medical University , Yantai, ChinaDepartment of Respiratory and Critical Care, Emergency and Critical Care Medical Center, Beijing Shijitan Hospital, Capital Medical University , Beijing, ChinaDepartment of Respiratory and Critical Care, Emergency and Critical Care Medical Center, Beijing Shijitan Hospital, Capital Medical University , Beijing, ChinaDepartment of Neurosurgery, Beijing Shijitan Hospital, Capital Medical University , Beijing, ChinaDepartment of Respiratory and Critical Care, Emergency and Critical Care Medical Center, Beijing Shijitan Hospital, Capital Medical University , Beijing, ChinaMedical Laboratory Center, The First Medical Centre, Chinese PLA General Hospital , Beijing, ChinaState Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences , Beijing, ChinaDepartment of Respiratory and Critical Care, Emergency and Critical Care Medical Center, Beijing Shijitan Hospital, Capital Medical University , Beijing, ChinaABSTRACT Cryptococcus gattii (C. gattii) is emerging as a life-threatening fungus worldwide. However, few data were available in China. In this study, 27 isolates and 32 patient information were collected from several hospitals in China, together with previously reported data (80 cases), to describe the geographic distribution of C. gattii. Molecular identification and genetic diversity analysis of the isolates were conducted using multilocus sequence typing, while the microbiological and virulence characteristics were explored through in vitro phenotypic tests and in vivo animal experiments. The findings revealed that patients infected with C. gattii were mainly immunocompetent males, with most showing symptoms of central nervous system involvement. Isolated strains were predominantly distributed in tropical and subtropical regions, with VGI genotype predominance. These strains exhibited marked genetic diversity, identifying 25 distinct sequence types (STs) among the 57 isolates (available data), including three novel STs (ST565, ST567, and ST568). In vitro assays unveiled significant differences between VGI and VGII in growth capacity at 39°C, capsule diameter, melanin production, UV resistance, and antioxidative capacity, with VGII displaying greater resilience. Integrating animal experiments and clinical prognosis showed that pathogenicity did not directly correlate with in vitro virulence phenotypes or molecular genotypes, underscoring virulence’s complexity. Furthermore, histopathological analysis suggested that lung tissue damage might primarily contribute to mouse mortality, particularly with more pathogenic strains causing extensive lung tissue damage. Our study has the potential to provide valuable data for a comprehensive understanding of the microbiological characteristics of C. gattii in China. IMPORTANCE Our study indicates that the molecular typing of Cryptococcus gattii is unrelated to virulence. The integration of animal experiments and clinical prognosis demonstrated that pathogenicity did not exhibit a direct correlation with in vitro virulence phenotypes or molecular genotypes, emphasizing the intricate nature of virulence. In conclusion, our research holds the potential to provide valuable insights into understanding the microbiological attributes of C. gattii in China.https://journals.asm.org/doi/10.1128/spectrum.02443-23Cryptococcus gattiimolecular epidemiologyvirulencemulti-center study
spellingShingle Xuelei Zang
Weixin Ke
Yemei Huang
Chen Yang
Jialin Song
Hengyu Deng
Meng Zhou
Qiqi Wang
Yangyu Zhou
Bin Dai
Jin Qian
Dingxia Shen
Linqi Wang
Xinying Xue
Virulence profiling of Cryptococcus gattii isolates in China: insights from a multi-center study
Microbiology Spectrum
Cryptococcus gattii
molecular epidemiology
virulence
multi-center study
title Virulence profiling of Cryptococcus gattii isolates in China: insights from a multi-center study
title_full Virulence profiling of Cryptococcus gattii isolates in China: insights from a multi-center study
title_fullStr Virulence profiling of Cryptococcus gattii isolates in China: insights from a multi-center study
title_full_unstemmed Virulence profiling of Cryptococcus gattii isolates in China: insights from a multi-center study
title_short Virulence profiling of Cryptococcus gattii isolates in China: insights from a multi-center study
title_sort virulence profiling of cryptococcus gattii isolates in china insights from a multi center study
topic Cryptococcus gattii
molecular epidemiology
virulence
multi-center study
url https://journals.asm.org/doi/10.1128/spectrum.02443-23
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