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

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.

过去二十年间，多起真菌暴发疫情相继发生，其中备受关注的“温哥华岛”与“太平洋西北地区”疫情由格特隐球菌（Cryptococcus gattii）引发，该疫情已波及数百名原本健康的人类与动物。同期，在该物种天然分布的热带与亚热带气候区之外的多个区域，C. gattii也引发了多起额外的病例聚集事件。所有此类疫情的病原体均属于格特隐球菌此前极为罕见的AFLP6/VGII基因型，然而此类暴发分支的起源始终成谜。本研究基于AFLP（扩增片段长度多态性）与多组MLST（多位点序列分型，Multi-Locus Sequence Typing）数据集，结合系统发育与重组分析以及溯祖基因谱系分析，证实此类疫情起源于巴西北部原生雨林中一个具有高度重组特性的格特隐球菌种群。由此可见，当前具有致病性的格特隐球菌AFLP6/VGII暴发谱系，源自南美洲境内的交配事件，随后扩散至温带区域并引发人类与动物的严重感染。