The emerging pathogen Cryptococcus gattii causes life-threatening disease in both immunocompetent and immunocompromised hosts. Molecular studies have identified four major molecular types (VGI-VGIV), with VGII being associated with outbreaks in North America and Australia. More recently, the molecular type VGIII has attracted attention, causing cryptococcosis in otherwise healthy human and animals. This recent emergence demonstrates the need to expand our knowledge about the genetics and epidemiology of this important pathogen and to correlate animal infection, environmental niches and human disease occurrence. To gain insides into the population genetic structure of this primary pathogen, clinical, environmental and veterinary isolates recovered from eight countries (Australia, Colombia, Guatemala, Mexico, New Zealand, Paraguay, USA and Venezuela) were subjected to multilocus sequence typing (MLST) and whole genome sequencing (WGS). Differences in virulence among the isolates were identified in a murine model of infection, and variation of antifungal susceptibility profiles were established against six drugs. Both MLST and WGS grouped all studied VGIII isolates in four divergent sub-populations, with most of the isolates being placed into two main clades, corresponding either with serotype B or C. Each of those two major groups contained clinical, environmental and veterinary samples. The global population of C. gattii molecular type VGIII was genetically highly diverse, whit minor differences among countries, source of isolation, serotype or mating type. Low or no recombination was found between the two major groups, serotype B and C. Overall, serotype B isolates were more virulent than serotype C isolates and caused mainly pulmonary cryptococcosis. However, serotype B isolates were more susceptible to azoles than serotype C isolates. Although C. gattii VGIII is widely spread in the Americas, with sporadic cases occurring elsewhere, WGS revealed Mexico and USA as a possible origin of the serotype B and Colombia as possible origin of the serotype C VGIII populations.
Less...