Molecular epidemiology and microbiological characteristics of Cryptococcus gattii VGII isolates from China

PLoS Negl Trop Dis. 2022 Feb 23;16(2):e0010078. doi: 10.1371/journal.pntd.0010078. eCollection 2022 Feb.

Abstract

Cryptococcus gattii (C. gattii) is a fungal pathogen that once caused an outbreak of cryptococcosis on Vancouver Island, and had spread worldwide, while few data were available in China. In this study, seven clinical isolates of C. gattii VGII were collected from 19 hospitals, Multi-locus Sequence Typing (MLST) analysis and whole-genome sequencing (WGS) was performed, combined with published data for phylogenetic analysis. In addition, in vitro antifungal susceptibility testing, phenotypic analysis, and in vivo virulence studies were performed, subsequently, histopathological analysis of lung tissue was performed. C.gattii VGII infected patients were mainly immunocompetent male, and most of them had symptoms of central nervous system (CNS) involvement. MLST results showed that isolates from China exhibited high genetic diversity, and sequence type (ST) 7 was the major ST among the isolates. Some clinical isolates showed a close phylogenetic relationship with strains from Australia and South America. All clinical isolates did not show resistance to antifungal drugs. In addition, there was no correlation between virulence factors (temperature, melanin production, and capsule size) and virulence while in vivo experiments showed significant differences in virulence among strains. Lung fungal burden and damage to lung tissue correlated with virulence, and degree of damage to lung tissue in mice may highlight differences in virulence. Our work seeks to provide useful data for molecular epidemiology, antifungal susceptibility, and virulence differences of C. gattii VGII in China.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antifungal Agents
  • Cryptococcosis* / microbiology
  • Cryptococcus gattii*
  • Genotype
  • Humans
  • Male
  • Mice
  • Molecular Epidemiology
  • Multilocus Sequence Typing
  • Phylogeny

Substances

  • Antifungal Agents

Grants and funding

This study was supported by National Key RESEARCH and development Program (XY.X, 2021YFC2302100), Beijing Natural Science Foundation (XY.X, 7192088), Excellent talents in Beijing “Youth top individual” (XY.X, 2019YXBJ1), Capital’s Funds for Health Improvement and Research (XY.X, 2020-2Z-2086), and Beijing Hospitals Authority Clinical medicine Development of special funding support (XY.X, XMLX202115). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.