Genomic epidemiology and phylogenomics of Magnusiomyces clavatus: a comparative analysis of novel italian and publicly available genomes

Background – Magnusiomyces clavatus is an emerging fungal pathogen primarily infecting immunocompromised patients hospitalized in hematological wards. Its remarkable genetic homogeneity makes high-resolution phylogenetic analysis challenging, hindering efforts to accurately discriminate strains and complicating epidemiological surveillance, particularly in the context of hospital outbreaks. Methods – In this study, we provide the most comprehensive phylogenomic framework to date for this species by analyzing a dataset of 62 whole-genome sequences, including four novel genomes from clinical and environmental strains recovered in a large hospital in southern Italy. Results – Using a pangenome graph-based variant calling strategy on 1, 624 high-quality single nucleotide polymorphisms, we delineated eight genetically distinct clades (A-H) that accurately reflect the geo-epidemiological history of this fungus. Population structure analysis revealed significant genetic differentiation among geographically separated populations, suggesting localized diversification. Furthermore, only the MATα idiomorph was identified across strains, supporting the highly clonal nature of M. clavatus. Finally, comparative mitogenomic analysis revealed 43 conserved translational bypass (byps) elements and identified four possible mitotypes based on presence or absence of specific inverted regions. Conclusions – This work provides a robust, high-resolution framework for future genomic epidemiology studies and outbreak investigations of this important emerging fungal pathogen.