Summary
Researchers developed an engineered budding-yeast system to test resistance-conferring mutations in genes from several pathogenic fungi. They also used random mutagenesis to identify new candidate mutations.
Researchers at Université Laval have developed a budding-yeast system for testing mutations linked to drug resistance in several pathogenic fungi. In a bioRxiv preprint posted on September 22, 2026, the team reports that the system reproduced known resistance phenotypes and helped identify new resistance-conferring mutations through random mutagenesis.
The approach moves fungal genes into Saccharomyces cerevisiae, a yeast with extensive genetic tools. That lets researchers test gene variants in a laboratory host rather than constructing the same mutations directly in pathogenic fungi—a process the authors describe as time-consuming and laborious.
How the yeast system works
The researchers built expression plasmids carrying codon-optimized versions of the fungal genes ERG3, ERG6 and ERG11. The genes came from Candida albicans, Candidozyma auris, Nakaseomyces glabratus, Candida parapsilosis and Candida tropicalis. The system also includes CYP51A and CYP51B from Aspergillus fumigatus.
They paired these plasmids with S. cerevisiae host strains in which the corresponding native ERG genes had either been deleted or placed under a repressible promoter. When expressed from the yeast’s native promoters, the introduced fungal gene versions complemented the function of the native genes. This provides a way to test whether a fungal gene variant can perform its basic role in the yeast host while researchers assess its resistance phenotype.
Reproducing and finding mutations
As a check on the platform, the team recreated previously reported resistance-conferring mutations and found that expression in S. cerevisiae reproduced known resistance phenotypes. They then tested corresponding mutations across gene orthologues—the versions of a gene found in different species—and reported that most resistance phenotypes were conserved.
The researchers also used random mutagenesis as a proof of concept to discover new resistance-conferring mutations. Because the work uses the genetic toolkit available for S. cerevisiae, the authors say mutants can be constructed and screened in fewer experimental steps, increasing throughput compared with introducing mutations in pathogenic fungi.
The system could make it easier to investigate how particular gene changes contribute to fungal resistance and to compare those effects across species. The study describes a laboratory research platform, rather than a clinical test for guiding treatment. The work is available as a bioRxiv preprint.