Insights into the origin, hybridisation and adaptation of Candida metapsilosis hybrid pathogens.

Hybridisation is a source of genetic diversity, can drive adaptation to new niches and has been found to be a frequent event in lineages harbouring pathogenic fungi. However, little is known about the genomic implications of hybridisation nor its impact on pathogenicity-related traits. A common limitation for addressing these questions is the narrow representativity of sequenced genomes, mostly corresponding to strains isolated from infected patients. The opportunistic human pathogen Candida metapsilosis is a hybrid that descends from the crossing between unknown parental lineages. Here, we sequenced the genomes of five new C. metapsilosis isolates, one representing the first African isolate for this species, and four environmental isolates from marine niches. Our comparative genomic analyses, including a total of 29 sequenced strains, shed light on the phylogenetic relationships between C. metapsilosis hybrid isolates and show that environmental strains are closely related to clinical ones and belong to different clades, suggesting multiple independent colonisations. Furthermore, we identify a new diverging clade likely emerging from the same hybridisation event that originated two other previously described hybrid clades. Lastly, we evaluate phenotypes relevant during infection such as drug susceptibility, thermotolerance or virulence. We identify low drug susceptibility phenotypes which we suggest might be driven by loss of heterozygosity events in key genes. We discover that thermotolerance is mainly clade-dependent and find a correlation with the faecal origin of some strains which highlights the adaptive potential of the fungus as commensal.