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Published on: December 28, 2017
Comparative genomic analysis of clinically relevant human skin-associated fungi
Sofie Agerbæk1, Knud Nor Nielsen2, Julie B K Sølberg3
1Department of Dermatology, Zealand University Hospital, Roskilde, Denmark.
Abstract:
Fungal skin infections represent a significant global health burden, affecting approximately one billion people annually. Despite their prevalence and major global health impact, the molecular mechanisms underlying pathogenicity remain largely uncharacterized. Here we present the genomes of 66 fungal strains, representing highly prevalent and clinically relevant species associated with human skin infections. Using comparative genomics, we investigate whether the taxonomic groups in this collection of skin fungi differ in their genome architecture, metabolic capacity, secreted enzyme repertoires, adhesin content, and predicted virulence determinants. These analyses reveal substantial variation in genome size and gene contents, indicating genome compaction occurred as the fungi transitioned from free-living to host-associated lifestyles. We report two non-hybrid strains of Trichosporon ovoides, the causative agent of white piedra. Our analyses reveal substantial differences in metabolic adaptations across skin-associated fungi, corresponding to body-site and nutrient niches. Significant differences are also observed in the distribution of virulence factors and adhesins, which are imperative for biofilm formation and antifungal resistance. We discuss metabolic adaptation and virulence mechanisms revealed by our data in the context of clinical presentations, highlighting shared and lineage-specific signatures of adaptations. Together, these insights advance our understanding of skin-associated fungi and their mechanisms of infection.
Insights
This study decodes the genomes of 66 fungal strains causing skin infections. It reveals significant variations in genome structure and virulence factors, offering insights into fungal pathogenicity and adaptation to the human host.
Area of Science:
- Medical Mycology
- Genomics
- Infectious Diseases
Background:
- Fungal skin infections affect ~1 billion people globally, posing a significant health burden.
- The molecular mechanisms of fungal pathogenicity remain poorly understood.
- Comparative genomics offers a powerful approach to investigate fungal adaptation and virulence.
Purpose of the Study:
- To present and analyze the genomes of 66 fungal strains causing human skin infections.
- To investigate variations in genome architecture, metabolic capacity, and virulence factors among different fungal groups.
- To understand the molecular basis of fungal adaptation to host-associated lifestyles and infection.
Main Methods:
- Comparative genomics of 66 fungal strains from clinically relevant species.
- Analysis of genome size, gene content, metabolic pathways, secreted enzymes, adhesins, and virulence determinants.
- Investigation of genome compaction during transition from free-living to host-associated states.
Main Results:
- Substantial variation in genome size and gene content observed, suggesting genome compaction in host-associated fungi.
- Identification of two non-hybrid strains of Trichosporon ovoides.
- Significant differences in metabolic adaptations linked to body site and nutrient availability.
- Variations in virulence factors and adhesins crucial for biofilm formation and antifungal resistance.
Conclusions:
- Fungal skin pathogens exhibit diverse genome architectures and metabolic strategies tailored to specific niches.
- Virulence factors and adhesins play key roles in fungal infection and resistance.
- This genomic data advances understanding of fungal adaptation and pathogenicity in skin infections.
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