Cryptococcus gattii VGI Subtypes: Geographical Distribution, Molecular Traits, and Virulence Difference

Background: As a life-threatening fungus, Cryptococcus gattii (C gattii) species complex is emerging worldwide. However, the geographical distribution, molecular traits, and virulence difference are poorly characterized in China.Results: From 2011 to 2017, we collected 32 strains of C gattii from 18 hospitals across China, of which 27 [84·4%] strains molecular traits were profiled by whole-genome sequencing (WGS) and multi-locus sequence typing (MLST) and compared with strains previously described in China from 2006 to 2020. Totally 119 clinical cases caused by C gattii strains (87 in previous reports and 32 in our study) distributed widely in 20 provincial-level administrative regions of China, of which 114 strains molecular types were obtained. The majority molecular type was VGI (81/114, 71·1%) and the other was VGII (33/114, 28·9%). Four major subtypes of VGI (VGIa, VGIb, VGIc, and VGId) were revealed from global C gattii VGI (n=308), respectively accounting for 52·9% (163/308), 36·0% (111/308), 3·9% (12/308), and 4·2% (13/308). The other nine strains could not be assigned to these four subtypes clearly. Our clinical data suggested that VGIb cases had a worse clinical outcome than VGIa, which was consistent with in vitro and in vivo experiments. In addition, a candidate virulence SNP on SOD2 in VGIa was initially identified by comparing high-quality de novo reference genome.Conclusions: The geographical distribution of C gattii species complex was first described in China. C gattii VGI could be clearly segregated into four major subtypes based on genomics profiles and VGIb was more virulent than VGIa in China. Our study suggests the molecular type of C gattii is necessary for personalized treatment in clinic.