Clonality and α-a Recombination in the Australian Cryptococcus gattii VGII Population - An Emerging Outbreak in Australia

Abstract

Background Cryptococcus gattii is a basidiomycetous yeast that causes life-threatening disease in humans and animals. Within C. gattii, four molecular types are recognized (VGI to VGIV). The Australian VGII population has been in the spotlight since 2005, when it was suggested as the possible origin for the ongoing outbreak at Vancouver Island (British Columbia, Canada), with same-sex mating being suggested as the driving force behind the emergence of this outbreak, and is nowadays hypothesized as a widespread phenomenon in C. gattii. However, an in-depth characterization of the Australian VGII population is still lacking. The present work aimed to define the genetic variability within the Australian VGII population and determine processes shaping its population structure.Methodology/Principal FindingsA total of 54 clinical, veterinary and environmental VGII isolates from different parts of the Australian continent were studied. To place the Australian population in a global context, 17 isolates from North America, Europe, Asia and South America were included. Genetic variability was assessed using the newly adopted international consensus multi-locus sequence typing (MLST) scheme, including seven genetic loci: CAP59, GPD1, LAC1, PLB1, SOD1, URA5 and IGS1. Despite the overall clonality observed, the presence of MAT a VGII isolates in Australia was demonstrated for the first time in association with recombination in MATα-MAT a populations. Our results also support the hypothesis of a “smouldering” outbreak throughout the Australian continent, involving a limited number of VGII genotypes, which is possibly caused by a founder effect followed by a clonal expansion.Conclusions/SignificanceThe detection of sexual recombination in MATα-MAT a population in Australia is in accordance with the natural life cycle of C. gattii involving opposite mating types and presents an alternative to the same-sex mating strategy suggested elsewhere. The potential for an Australian wide outbreak highlights the crucial issue to develop active surveillance procedures.

Is Predominant Clonal Evolution a Common Evolutionary Adaptation to Parasitism in Pathogenic Parasitic Protozoa, Fungi, Bacteria, and Viruses?

“…Another one has been recorded from 1983 to 2009 in North and South America, in Europe and in Asia (Khayhan et al, 2013). C. gattii and C. neoformans also exhibit very typical near-clades (Tibayrenc and Ayala, 2014b), corroborated by various molecular markers, including AFLP, MLST, PCR fingerprinting, RAPD and RFLP, and strongly linked to serotypes (Bovers et al, 2008;Campbell et al, 2005;Campbell and Carter, 2006;Carriconde et al, 2011;Chaturvedi and Chaturvedi, 2011;Fraser et al, 2005;Khayhan et al, 2013;Lin and Heitman, 2006;Litvintseva and Mitchell, 2012;Ngamskulrungroj et al, 2009;Voelz et al, 2013;Xu, 2006a). In C. gattii, there are 4 'molecular types' (near-clades) I to IV.…”

“…In these two species, LD is observed between genetic types and serotypes (Campbell and Carter, 2006). In C. gattii, the clonal genotype responsible for the Vancouver epidemics has also been sampled in San Francisco, and is identical to the NIH 444 strain isolated in 1970 (Carriconde et al, 2011;Chaturvedi and Chaturvedi, 2011). It is supposed to have originated from Australia by 'same sex mating' .…”

Antifungal Drug Susceptibility and Phylogenetic Diversity among Cryptococcus Isolates from Dogs and Cats in North America

“…Dendrograms showing the genetic relationships among C. gattii isolates and among C. neoformans isolates were constructed using a software package (MEGA 5.05; Center for Evolutionary Medicine and Informatics, Tempe, AZ) based on maximum likelihood analysis of the concatenated seven ISHAM consensus MLST loci. Additional C. gattii strains included in the MLST analysis are listed in Table S1 in the supplemental material (15,28,(32)(33)(34)(35)(36)(37).…”

Medical and veterinary mycology

“…However, it was the discovery of the natural habitat of C. gattii in 1990 14 that provided a major impetus for research on the epidemiology and ecology of this fungus. These studies defined the epidemiology of these serious fungal infections in Australia 15 and elsewhere and through global collaborations, have revealed the origin of highly pathogenic strains and increased understanding of the molecular basis of cryptococcal pathogenicity 16,17 .…”