Global Population Genetic Analysis ofAspergillus fumigatus.
Aspergillus fumigatusis 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 ofA. fumigatusremains poorly understood. In this study, we analyzed 2,026A. fumigatusisolates from 13 countries in four continents using nine highly polymorphic microsatellite markers. Genetic cluster analyses suggest that our global sample ofA. fumigatusisolates 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 ofA. fumigatusare 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.IMPORTANCEThe genetic diversity and geographic structure of the human fungal pathogenA. fumigatushave 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 ofA. fumigatususing 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 thatA. fumigatuscontains 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.
Department of Biology, McMaster University, Hamilton, Ontario, Canada.
Eta Ebasi
EE
Ashu
Department of Medical Microbiology and Infectious Diseases, Canisius Wilhelmina Hospital, Nijmegen, Netherlands.
Ferry
F
Hagen
Department of Medical Mycology, Vallabhbhai Patel Chest Institute, University of Delhi, Delhi, India.
Anuradha
A
Chowdhary
Department of Medical Microbiology and Infectious Diseases, Canisius Wilhelmina Hospital, Nijmegen, Netherlands; Center of Expertise in Mycology, Radboud University Medical Center, Canisius Wilhelmina Hospital, Nijmegen, Netherlands.
Jacques F
0000-0003-3253-6080
JF
Meis
Department of Biology, McMaster University, Hamilton, Ontario, Canada; Public Research Laboratory and Institute of Tropical Diseases Research, Hainan Medical University, Haikou, Hainan, China.
Jianping
0000-0003-2915-2780
J
Xu
Aspergillus fumigatus; ecological structure; gene flow; genetic populations; genetic recombination; geographic structure; microsatellite markers; triazole drug selection