Ashu Eta Ebasi, Hagen Ferry, Chowdhary Anuradha, Meis Jacques F, Xu Jianping
Department of Biology, McMaster University, Hamilton, Ontario, Canada.
Department of Medical Microbiology and Infectious Diseases, Canisius Wilhelmina Hospital, Nijmegen, Netherlands.
mSphere. 2017 Feb 1;2(1). doi: 10.1128/mSphere.00019-17. eCollection 2017 Jan-Feb.
is a ubiquitous opportunistic fungal pathogen capable of causing invasive aspergillosis, a globally distributed disease with a mortality rate of up to 90% in high-risk populations. Effective control and prevention of this disease require a thorough understanding of its epidemiology. However, despite significant efforts, the global molecular epidemiology of remains poorly understood. In this study, we analyzed 2,026 isolates from 13 countries in four continents using nine highly polymorphic microsatellite markers. Genetic cluster analyses suggest that our global sample of isolates belonged to eight genetic clusters, with seven of the eight clusters showing broad geographic distributions. We found common signatures of sexual recombination within individual genetic clusters and clear evidence of hybridization between several clusters. Limited but statistically significant genetic differentiations were found among geographic and ecological populations. However, there was abundant evidence for gene flow at the local, regional, and global scales. Interestingly, the triazole-susceptible and triazole-resistant populations showed different population structures, consistent with antifungal drug pressure playing a significant role in local adaptation. Our results suggest that global populations of are shaped by historical differentiation, contemporary gene flow, sexual reproduction, and the localized antifungal drug selection that is driving clonal expansion of genotypes resistant to multiple triazole drugs. The genetic diversity and geographic structure of the human fungal pathogen have been the subject of many studies. However, most previous studies had relatively limited sample ranges and sizes and/or used genetic markers with low-level polymorphisms. In this paper, we characterize a global collection of strains of using a panel of 9 highly polymorphic microsatellite markers. Using these markers, we analyze 2,026 isolates, which is ~3 times the number of isolates reported so far in previous studies. Our analyses suggest that contains historically differentiated genetic populations but that its evolution is significantly impacted by contemporary forces such as widespread gene flow and local antifungal drug pressure. In the wake of a global rise in resistance to azoles in fungal pathogens, our findings should aid in developing management strategies to mitigate current increases to azole resistance.
是一种普遍存在的机会性真菌病原体，能够引起侵袭性曲霉病，这是一种全球分布的疾病，在高危人群中的死亡率高达90%。有效控制和预防这种疾病需要全面了解其流行病学。然而，尽管付出了巨大努力，其全球分子流行病学仍知之甚少。在本研究中，我们使用9个高度多态性的微卫星标记分析了来自四大洲13个国家的2026株分离株。遗传聚类分析表明，我们的全球分离株样本属于8个遗传簇，其中8个簇中的7个显示出广泛的地理分布。我们在单个遗传簇中发现了有性重组的共同特征，并有几个簇之间杂交的明确证据。在地理和生态种群之间发现了有限但具有统计学意义的遗传分化。然而，在局部、区域和全球尺度上有大量基因流动的证据。有趣的是，对三唑敏感和耐药的种群表现出不同的种群结构，这与抗真菌药物压力在局部适应中发挥重要作用一致。我们的结果表明，全球种群是由历史分化、当代基因流动、有性繁殖以及驱动对多种三唑药物耐药的基因型克隆扩张的局部抗真菌药物选择所塑造的。人类真菌病原体的遗传多样性和地理结构一直是许多研究的主题。然而，以前的大多数研究样本范围和规模相对有限，和/或使用多态性水平较低的遗传标记。在本文中，我们使用一组9个高度多态性的微卫星标记对全球收集的菌株进行了表征。使用这些标记，我们分析了2026株分离株，这大约是以前研究中报道的分离株数量的3倍。我们的分析表明，包含历史上分化的遗传种群，但其进化受到当代力量的显著影响，如广泛的基因流动和局部抗真菌药物压力。在真菌病原体对唑类耐药性全球上升的情况下，我们的发现应有助于制定管理策略，以减轻目前唑类耐药性的增加。
