Phylogenomic Placement of American Southwest-Associated Clinical and Veterinary Isolates Expands Evidence for Distinct Cryptococcus gattii VGVI

Abstract

Whole-genome sequencing has advanced our understanding of the population structure of the pathogenic species complex Cryptococcus gattii, which has allowed for the phylogenomic specification of previously described major molecular type groupings and novel lineages. Recently, isolates collected in Mexico in the 1960s were determined to be genetically distant from other known molecular types and were classified as VGVI. We sequenced four clinical isolates and one veterinary isolate collected in the southwestern United States and Argentina from 2012 to 2021. Phylogenomic analysis groups these genomes with those of the Mexican VGVI isolates, expanding VGVI into a clade and establishing this molecular type as a clinically important population. These findings also potentially expand the known Cryptococcus ecological range with a previously unrecognized endemic area.

Global Analyses of Multi-Locus Sequence Typing Data Reveal Geographic Differentiation, Hybridization, and Recombination in the Cryptococcus gattii Species Complex

“…These lineages are frequently referred to as molecular types and increasingly more as species [ 42 ]. Formally, the C. gattii species complex is divided into six distinct lineages (VGI, VGII, VGIII, VGIV, VGV, and VGVI) [ 3 , 43 , 44 ]. In this report, we focus on the four lineages with isolates represented in the International Fungal Multi Locus Sequence Typing (IFMLST) database.…”

Pulmonary Cryptococcosis

“…Additional Cryptococcus species names have been suggested [18] but in practice, the nomenclature C. neoformans or C. gattii complex are used in most settings [19]. Genotypes of C. neoformans include VNI, VNBI, VNII, VNBII, VNIII and VNIV and C. gattii genotypes encompass VGI, VGII, VGIIa, VGIIb, VGIIc, VGIII, VGIV, VGV and VGIV (Table 1) [18,19], with the latter two C. gattii genotypes, (VGV and VGVI) only recently recognised [20,21]. An alternative classification of the pathogenic Cryptococcus species into seven unique species within a C. neoformans/C.…”

Genotyping Analysis of Cryptococcus deuterogattii and Correlation with Virulence Factors and Antifungal Susceptibility by the Clinical and Laboratory Standards Institute and the European Committee on Antifungal Susceptibility Testing Methods

“…Nevertheless, this proposal remains under discussion [ 5 , 6 , 7 ]. Furthermore, the C. gattii species complex (CGSC) diversity spectrum is ongoing, as indicated by the recent discovery of VGV and VGVI genotypes in environmental isolates from Africa [ 8 ] and by the increase in the number of data confirming C. decagatti as VGVI [ 8 , 9 , 10 ].…”

“…The isolates of the VGV lineage were recovered from Zambian woodland environments in association with the nitrogen-rich middens of a small mammal known as Hyrax [ 8 ]. Otherwise, C. decagatti has already been obtained from clinical cases and a veterinary isolate [ 8 , 10 ].…”