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

Amelia E Barber1,2, Tongta Sae-Ong3, Kang Kang3

  • 1Research Group Fungal Septomics, Leibniz Institute of Natural Product Research and Infection Biology-Hans Knöll Institute, Jena, Germany.

Nature Microbiology
|November 25, 2021
PubMed

Insights

Genomic analysis of Aspergillus fumigatus reveals significant diversity between clinical and environmental strains. This genetic variation influences virulence and antifungal resistance, crucial for managing invasive fungal infections.

Area of Science:

  • Mycology
  • Genomics
  • Infectious Diseases

Background:

  • Aspergillus fumigatus is a major opportunistic fungal pathogen causing over 300,000 invasive infections annually worldwide.
  • Limited understanding of genomic diversity hinders comprehension of its virulence and antifungal resistance.
  • A comprehensive genomic survey is needed to explore the relationship between clinical and environmental isolates.

Purpose of the Study:

  • To define the pan-genome of Aspergillus fumigatus using a large, globally sampled collection of genomes.
  • To investigate the genomic diversity and its contribution to virulence and antifungal drug resistance.
  • To identify genetic variations associated with clinical isolates and triazole resistance.

Main Methods:

  • Sequencing and analysis of 300 Aspergillus fumigatus genomes (83 clinical, 217 environmental).
  • Pan-genome analysis to identify core and accessory genes.
  • Genome-wide association studies (GWAS) to link genetic variation with phenotypes.

Main Results:

  • Defined the Aspergillus fumigatus pan-genome, identifying 7,563 core orthogroups (69%) and 3,344 accessory orthogroups (16-22% variation).
  • Clinical isolates showed enrichment in a genetic cluster with more accessory genes, including those for transport, iron-binding, and metabolism.
  • Identified genomic variations linked to clinical isolation and triazole resistance, and characterized variation in virulence factors.

Conclusions:

  • The genomic diversity of Aspergillus fumigatus is substantial, with significant accessory gene content contributing to pathogenic versatility.
  • Moving beyond a single reference genome is essential for understanding A. fumigatus pathogenicity.
  • This research provides a foundation for improved diagnostics and management of invasive aspergillosis.

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