Population Genetic Analysis Reveals a High Genetic Diversity in the Brazilian Cryptococcus gattii VGII Population and Shifts the Global Origin from the Amazon Rainforest to the Semi-arid Desert in the Northeast of Brazil

Abstract

Cryptococcus neoformans and Cryptococcus gattii are responsible globally for almost one million cryptococcosis cases yearly, mostly in immunocompromised patients, such as those living with HIV. Infections due to C. gattii have mainly been described in tropical and subtropical regions, but its adaptation to temperate regions was crucial in the species evolution and highlighted the importance of this pathogenic yeast in the context of disease. Cryptococcus gattii molecular type VGII has come to the forefront in connection with an on-going emergence in the Pacific North West of North America. Taking into account that previous work pointed towards South America as an origin of this species, the present work aimed to assess the genetic diversity within the Brazilian C. gattii VGII population in order to gain new insights into its origin and global dispersal from the South American continent using the ISHAM consensus MLST typing scheme. Our results corroborate the finding that the Brazilian C. gattii VGII population is highly diverse. The diversity is likely due to recombination generated from sexual reproduction, as evidenced by the presence of both mating types in clinical and environmental samples. The data presented herein strongly supports the emergence of highly virulent strains from ancestors in the Northern regions of Brazil, Amazonia and the Northeast. Numerous genotypes represent a link between Brazil and other parts of the world reinforcing South America as the most likely origin of the C. gattii VGII subtypes and their subsequent global spread, including their dispersal into North America, where they caused a major emergence.

Conservation of Intracellular Pathogenic Strategy among Distantly Related Cryptococcal Species

“…The C. neoformans and C. gattii species diverged approximately 80 million to 100 million years ago, roughly correlating with the time of separation of Africa and South America, where these species originated, respectively (2,(35)(36)(37)(38). Despite these species' long period of separation and geographical distribution, they are remarkably similar, such that they were considered the same species for over a century.…”

Two‐step method for isolating Cryptococcus species complex from environmental material using a new selective medium

“…Regional genetic diversity is essential in phylogenetic studies. Brazilian C. gattii VGII population was found with the highest diversity in the world, and the link between C. gattii VGII population in Brazil and other parts of the world indicates that Brazil is the origin of this subtype of C. gattii that spreads worldwide (Souto et al ., ). The survival of Cryptococcus cells within environmental amoebae had been demonstrated similar to the survival of Cryptococcus cells in macrophages, and some mechanisms, such as zinc homeostasis and polysaccharide accumulation, had been revealed related to the survival of intracellular Cryptococcus cells (Steenbergen et al ., ; Ribeiro et al ., ).…”

Differential In Vitro Cytokine Induction by the Species of Cryptococcus gattii Complex

“…Most knowledge about the immune response patterns against Cryptococcus species is derived from studies of C. neoformans species complex isolates performed with animal models and human cells (30)(31)(32)(33)(34). However, the interest in studying immune response patterns against the members of the C. gattii species complex has increased recently (28,29,(35)(36)(37)(38) due to evidence of genetic diversity, phenetic differences, and epidemiologic particularities among the species (1,18,(39)(40)(41). Based on these aspects, the present study hypothesized that the five species within the C. gattii complex have different abilities to induce cytokine production in human cells, a crucial step for the activation of host defense.…”