Cryptococcus gattii in North American Pacific Northwest: whole-population genome analysis provides insights into species evolution and dispersal.
Cryptococcus gattii in North American Pacific Northwest: whole-population genome analysis provides insights into species evolution and dispersal.
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DOI：
10.1128/mbio.01464-14
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发表时间：
2014-07-15
期刊：
影响因子：
6.4
通讯作者：
Meyer W
中科院分区：
文献类型：
--
作者：
Engelthaler DM;Hicks ND;Gillece JD;Roe CC;Schupp JM;Driebe EM;Gilgado F;Carriconde F;Trilles L;Firacative C;Ngamskulrungroj P;Castañeda E;Lazera Mdos S;Melhem MS;Pérez-Bercoff A;Huttley G;Sorrell TC;Voelz K;May RC;Fisher MC;Thompson GR 3rd;Lockhart SR;Keim P;Meyer W
在北美太平洋西北部（PNW）温带地区出现不同的隐球菌种群是令人惊讶的，因为该物种以前被认为仅限于热带和亚热带地区。除了一个新的栖息地生态位，占主导地位的新兴人口表现出增加的毒力，并导致原发性肺部疾病，而不是以前在其他地方看到的主要神经系统疾病。对118株格特隐球菌分离株进行了全基因组测序，包括PNW亚型和VGII分子型的全球多样性，以更好地确定导致PNW感染出现的自然来源和基因组适应。总体而言，VGII人口是高度多样化的，表现出大量的突变和重组事件，但是，从PNW的三个占主导地位的亚型是低多样性和完全克隆。尽管VGII菌株至少在五大洲发现，但所有遗传亚群都与南美洲的菌株有代表性或最密切相关。系统发育数据与从南美洲到北美洲和其他地方的多个扩散事件是一致的。众多的基因含量差异之间的紧急克隆和其他VGII谱系，包括基因可能与栖息地适应，毒力和病理学。也发现了可能的基因渗入的证据，从新生隐球菌变种。grubii，这是罕见的，在全球C. gattii，但存在于所有PNW种群。这些发现提供了更好的理解C. gattii在北美的进化，并支持在南美洲的广泛进化和传播。格特隐球菌于20世纪90年代末出现在温带北美太平洋西北部（PNW）。除了新的环境生态位，这些新出现的种群表现出更强的毒力，并导致不同的临床疾病模式。特别是，严重的肺部感染占主导地位，与神经系统疾病的表现，如以前在其他地方看到的。我们采用群体水平的全基因组测序和分析，以探讨PNW C. gattii群体的遗传关系和基因含量。我们提供的证据表明，PNW菌株起源于南美洲，并确定了许多基因可能与栖息地适应，毒力表达和临床表现。这些遗传特征的表征可能会导致改进此类真菌感染的诊断和治疗。数据表明，最近有多个C. gattii引入PNW。公共卫生警惕是必要的出现在该地区的C. gattii不被认为是地方病。
The emergence of distinct populations of Cryptococcus gattii in the temperate North American Pacific Northwest (PNW) was surprising, as this species was previously thought to be confined to tropical and semitropical regions. Beyond a new habitat niche, the dominant emergent population displayed increased virulence and caused primary pulmonary disease, as opposed to the predominantly neurologic disease seen previously elsewhere. Whole-genome sequencing was performed on 118 C. gattii isolates, including the PNW subtypes and the global diversity of molecular type VGII, to better ascertain the natural source and genomic adaptations leading to the emergence of infection in the PNW. Overall, the VGII population was highly diverse, demonstrating large numbers of mutational and recombinational events; however, the three dominant subtypes from the PNW were of low diversity and were completely clonal. Although strains of VGII were found on at least five continents, all genetic subpopulations were represented or were most closely related to strains from South America. The phylogenetic data are consistent with multiple dispersal events from South America to North America and elsewhere. Numerous gene content differences were identified between the emergent clones and other VGII lineages, including genes potentially related to habitat adaptation, virulence, and pathology. Evidence was also found for possible gene introgression from Cryptococcus neoformans var. grubii that is rarely seen in global C. gattii but that was present in all PNW populations. These findings provide greater understanding of C. gattii evolution in North America and support extensive evolution in, and dispersal from, South America. Cryptococcus gattii emerged in the temperate North American Pacific Northwest (PNW) in the late 1990s. Beyond a new environmental niche, these emergent populations displayed increased virulence and resulted in a different pattern of clinical disease. In particular, severe pulmonary infections predominated in contrast to presentation with neurologic disease as seen previously elsewhere. We employed population-level whole-genome sequencing and analysis to explore the genetic relationships and gene content of the PNW C. gattii populations. We provide evidence that the PNW strains originated from South America and identified numerous genes potentially related to habitat adaptation, virulence expression, and clinical presentation. Characterization of these genetic features may lead to improved diagnostics and therapies for such fungal infections. The data indicate that there were multiple recent introductions of C. gattii into the PNW. Public health vigilance is warranted for emergence in regions where C. gattii is not thought to be endemic.