MEM INST OSWALDO CRUZ, RIO DE JANEIRO, Vol. 113 | 2018
PAGES: DOI: 10.1590/0074-02760170473 Review
Advances in Cryptococcus genomics: insights into the evolution of pathogenesis

Christina A Cuomo1,+, Johanna Rhodes2, Christopher A Desjardins1

1Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA, USA
2Department of Infectious Disease Epidemiology, Imperial College London, London, United Kingdom

Abstract

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.

Financial support: NIAID, NIH, DH and HS to the Broad Institute.
CAC and CAD were supported by the NIAID, NIH, DH and HS to the Broad Institute (Grant No. U19AI110818); JR was supported by UK Medical Research Council (Grant MRC MR/K000373/1).
+ Corresponding author: This e-mail address is being protected from spambots. You need JavaScript enabled to view it.
Received 31 October 2017
Accepted 17 December 2017

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