Aspergillus fumigatus pan-genome analysis identifies genetic variants associated with human infection

Author:

AE Barber1,2*, T Sae-Ong3, K Kang3, B Seelbinder3, J Li4,5, G Walther6, G Panagiotou3,7, O Kurzai1,8

Author address:

1Research Group Fungal Septomics, Leibniz-HKI, Jena, Germany

2Junior Research Group Fungal Informatics, Leibniz-HKI, Jena, Germany

3Research Group Systems Biology and Bioinformatics, Leibniz-HKI, Jena, Germany

4Department of Infectious Diseases and Public Health, City University of Hong Kong, Hong Kong, China

5School of Data Science, City University of Hong Kong, Hong Kong, China

6National Reference Center for Invasive Fungal Infections, Leibniz-HKI, Jena, Germany

7Department of Medicine, University of Hong Kong, Hong Kong, China

8Institute for Hygiene and Microbiology, University of Würzburg, Würzburg, Germany

Full conference title:

10th Advances Against Aspergillosis and Mucormycosis

Date: 2 February 2022

Abstract:

Purpose:

Aspergillus fumigatus is an environmental saprobe and opportunistic human pulmonary pathogen. Infections caused by A. fumigatus are particularly problematic in immunocompromised patient populations, but new risk cohorts are continuing to emerge, and antifungal resistance rates are increasing. Despite the significant and increasing burden of these infections, a comprehensive genomic survey of Aspergillus fumigatus has been lacking. Our objective was to define the genome-level relationship between the environmental isolates in their native niche and those capable of causing human infection, as well as identify genetic variation associated with clinical strains and drug resistance.

 

Methods:

The genomes of 300 A. fumigatus environmental and clinical isolates were analyzed using reference-guided and de novo techniques. 252 of the isolates analyzed were sequenced by us and originate from Germany while the remaining 48 were previously sequenced and from a global distribution.

 

Results:

In this study, we define the pangenome and find that of the 10,907 unique orthogroups, 7,563 (69%) are core and found in all isolates, while 3,344 show presence/absence variation, representing 16-22% of each isolate’s genome. Using this large genomic dataset of environmental and clinical samples, we found an enrichment for clinical isolates in a genetic cluster whose genomes also contain more accessory genes, including more transmembrane transporters, proteins with iron-binding activity, and genes involved in both carbohydrate and amino acid metabolism. Finally, we leverage the power of genome-wide association to identify genomic variation associated with clinical isolates and triazole resistance as well as characterize genetic variation in known virulence factors.

 

Conclusion:

The broad genomic diversity observed in A. fumigatus suggests that a single reference strain is not sufficient to capture all the genetic diversity present and fully understand its pathogenic versatility.

Abstract Number: 38

Conference Year: 2022

Link to conference website: https://aaam2022.org/

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