Correlating Genotype and Phenotype in the Asexual Yeast Candida orthopsilosis Implicates ZCF29 in Sensitivity to...

Area of Science:

• Medical Mycology
• Population Genomics
• Antimicrobial Resistance

Background:

• Candida orthopsilosis is a diploid asexual yeast responsible for human infections.
• Most C. orthopsilosis strains originate from hybridizations between distinct parent lineages.
• Understanding genotype-phenotype correlations is crucial for managing C. orthopsilosis infections.

Purpose of the Study:

• To correlate genotypic variations with phenotypic traits in Candida orthopsilosis isolates.
• To identify high-impact genetic variants associated with specific phenotypes.
• To investigate the functional role of a specific gene variant using CRISPR-Cas9 editing.

Main Methods:

• Population genomics data analysis of 28 C. orthopsilosis isolates.
• Cosine similarity scores to identify variants correlating with phenotypes.
• CRISPR-Cas9 gene editing to validate the effect of a specific Single Nucleotide Polymorphism (SNP).

Main Results:

• Identified 65 potentially high-impact variants, including 19 SNPs affecting critical gene regions.
• A premature stop codon in both alleles of ZCF29 in one isolate correlated with nystatin and caffeine sensitivity.
• CRISPR-Cas9 introduction of the ZCF29 stop codon induced sensitivity to ketoconazole and caffeine, but not nystatin.

Conclusions:

• Genomic variants can be associated with phenotypes in asexual Candida species.
• A specific ZCF29 gene variant influences drug susceptibility in C. orthopsilosis.
• The study highlights the feasibility and limitations of exploring genomic variation for phenotype association.