Farrer Rhys A, Voelz Kerstin, Henk Daniel A, Johnston Simon A, Fisher Matthew C, May Robin C, Cuomo Christina A
Genome Sequencing and Analysis Program, The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
Department of Infectious Disease Epidemiology, School of Public Health, Imperial College London, London W2 1PG, UK.
Philos Trans R Soc Lond B Biol Sci. 2016 Dec 5;371(1709). doi: 10.1098/rstb.2016.0021.
Emerging fungal pathogens cause an expanding burden of disease across the animal kingdom, including a rise in morbidity and mortality in humans. Yet, we currently have only a limited repertoire of available therapeutic interventions. A greater understanding of the mechanisms of fungal virulence and of the emergence of hypervirulence within species is therefore needed for new treatments and mitigation efforts. For example, over the past decade, an unusual lineage of Cryptococcus gattii, which was first detected on Vancouver Island, has spread to the Canadian mainland and the Pacific Northwest infecting otherwise healthy individuals. The molecular changes that led to the development of this hypervirulent cryptococcal lineage remain unclear. To explore this, we traced the history of similar microevolutionary events that can lead to changes in host range and pathogenicity. Here, we detail fine-resolution mapping of genetic differences between two highly related Cryptococcus gattii VGIIc isolates that differ in their virulence traits (phagocytosis, vomocytosis, macrophage death, mitochondrial tubularization and intracellular proliferation). We identified a small number of single site variants within coding regions that potentially contribute to variations in virulence. We then extended our methods across multiple lineages of C. gattii to study how selection is acting on key virulence genes within different lineages.This article is part of the themed issue 'Tackling emerging fungal threats to animal health, food security and ecosystem resilience'.
新出现的真菌病原体给整个动物界带来了日益加重的疾病负担，包括人类发病率和死亡率的上升。然而，我们目前可用的治疗干预手段有限。因此，为了开发新的治疗方法并做出缓解努力，需要更深入地了解真菌毒力机制以及物种内高毒力的出现情况。例如，在过去十年中，一种最初在温哥华岛被发现的异常谱系的加氏隐球菌，已经扩散到加拿大大陆和太平洋西北部，感染原本健康的个体。导致这种高毒力隐球菌谱系出现的分子变化仍不清楚。为了探究这一问题，我们追溯了可能导致宿主范围和致病性变化的类似微进化事件的历史。在这里，我们详细描述了两个高度相关的加氏隐球菌VGIIc分离株之间的遗传差异的精细图谱，这两个分离株在毒力特征（吞噬作用、胞吐作用、巨噬细胞死亡、线粒体管状化和细胞内增殖）方面存在差异。我们在编码区域内鉴定出少量单一位点变异，这些变异可能导致毒力差异。然后，我们将方法扩展到加氏隐球菌的多个谱系，以研究选择如何作用于不同谱系中的关键毒力基因。本文是主题为“应对新出现的真菌对动物健康、粮食安全和生态系统复原力的威胁”的特刊的一部分。
