Ancient Dispersal of the Human Fungal Pathogen Cryptococcus gattii from the Amazon Rainforest

Abstract

Over the past two decades, several fungal outbreaks have occurred, including the high-profile ‘Vancouver Island’ and ‘Pacific Northwest’ outbreaks, caused by Cryptococcus gattii, which has affected hundreds of otherwise healthy humans and animals. Over the same time period, C. gattii was the cause of several additional case clusters at localities outside of the tropical and subtropical climate zones where the species normally occurs. In every case, the causative agent belongs to a previously rare genotype of C. gattii called AFLP6/VGII, but the origin of the outbreak clades remains enigmatic. Here we used phylogenetic and recombination analyses, based on AFLP and multiple MLST datasets, and coalescence gene genealogy to demonstrate that these outbreaks have arisen from a highly-recombining C. gattii population in the native rainforest of Northern Brazil. Thus the modern virulent C. gattii AFLP6/VGII outbreak lineages derived from mating events in South America and then dispersed to temperate regions where they cause serious infections in humans and animals.

Cryptococcus gattii Infections

“…The WGST data showed clearly that the VGIIc genotype responsible for the most recent infections in the Pacific Northwest is genetically distinct from both VGIIa and VGIIb Vancouver Island outbreak subtypes and suggest that all three subtypes are equally distinct from each other (52). Similar findings based on multilocus sequence typing (MLST) and MLMT analyses, which have been confirmed based on WGST, have been reported recently (53)(54)(55). All studies suggest that the three subtypes have arisen as a result of recombination events that took place prior to their introduction into the Pacific Northwest.…”

“…These findings agree with a recent comprehensive, global study of VGII strains, which traced the origin of both outbreak subgenotypes VGIIa and VGIIb back to an ancestral C. gattii strain, LMM645, from the Amazon rainforest. This study revealed the presence of the VGIIa and VGIIb genotypes and MATa and MAT␣ strains in Brazil and showed clear evidence for recombination among the Brazilian C. gattii population (53).…”

“…It is highly reproducible, and the primers used to amplify the microsatellites are species specific. This technique distinguishes all four major molecular types of C. gattii and has enabled the tracing of highly virulent strains (see below) (53,66,67).…”

“…AFLP analysis of clinical isolates revealed that they are geographically restricted, highly clonal, and of low fertility (53,116,117). Subsequent extensive testing of isolates from single tree hollows by AFLP analysis revealed that recombination is occurring in both MATa and MAT␣ or MAT␣-only populations (118).…”

A Model CNS Fungal Infection: Cryptococcal Meningitis

“…Until recently, evidence was balanced between the likeliest candidates: South America, Africa and Australia (which all had evidence of recombination and genetic diversity). However, recently, the case for South America has strengthened [29], due to the discovery of a strain displaying a basal genetic lineage in virgin Amazonian rainforest, where contamination from imported woods is thought extremely unlikely [84].…”