Cuomo Christina A, Rhodes Johanna, Desjardins Christopher A
Broad Institute, Massachusetts, United States.
Department of Infectious Disease Epidemiology, Imperial College London, London, United Kingdom.
Mem Inst Oswaldo Cruz. 2018;113(7):e170473. doi: 10.1590/0074-02760170473. Epub 2018 Feb 19.
Cryptococcus species are the causative agents of cryptococcal meningitis, a significant source of mortality in immunocompromised individuals. Initial work on the molecular epidemiology of this fungal pathogen utilized genotyping approaches to describe the genetic diversity and biogeography of two species, Cryptococcus neoformans and Cryptococcus gattii. Whole genome sequencing of representatives of both species resulted in reference assemblies enabling a wide array of downstream studies and genomic resources. With the increasing availability of whole genome sequencing, both species have now had hundreds of individual isolates sequenced, providing fine-scale insight into the evolution and diversification of Cryptococcus and allowing for the first genome-wide association studies to identify genetic variants associated with human virulence. Sequencing has also begun to examine the microevolution of isolates during prolonged infection and to identify variants specific to outbreak lineages, highlighting the potential role of hyper-mutation in evolving within short time scales. We can anticipate that further advances in sequencing technology and sequencing microbial genomes at scale, including metagenomics approaches, will continue to refine our view of how the evolution of Cryptococcus drives its success as a pathogen.
隐球菌属是隐球菌性脑膜炎的病原体，在免疫功能低下的个体中是一个重要的死亡原因。对这种真菌病原体分子流行病学的初步研究利用基因分型方法来描述两种隐球菌，即新生隐球菌和格特隐球菌的遗传多样性和生物地理学。对这两个物种的代表进行全基因组测序，得到了参考基因组组装结果，从而能够开展一系列下游研究并提供基因组资源。随着全基因组测序的日益普及，现在这两个物种都已有数百个个体分离株进行了测序，从而对隐球菌的进化和多样化有了精细的了解，并使得首次能够开展全基因组关联研究来确定与人类致病性相关的基因变异。测序也已开始研究长期感染期间分离株的微观进化，并识别特定于暴发谱系的变异，突出了超突变在短时间尺度内进化中的潜在作用。我们可以预期，测序技术以及大规模测序微生物基因组（包括宏基因组学方法）的进一步进展，将不断完善我们对隐球菌进化如何推动其作为病原体取得成功的看法。
