Chromosome-scale CRISPR screening reveals secretory pathway genes as drivers of aneuploidy-mediated antifungal tolerance

Secretory pathway regulators SEC4 and YPT31 are necessary and sufficient for Candida albicans chromosome R–mediated azole tolerance, increasing ergosterol content in the cell membrane.

• Why it matters: The genetic drivers of beneficial aneuploidies are rarely pinpointed, and it is unclear why ChrR repeatedly arises after azole exposure or how it promotes tolerance.
• What they did: The study combined RNA-seq with parallel chromosome-wide CRISPRa and CRISPRi screens targeting ChrR genes, then used multiplexed CRISPR-dCas12a to test combinatorial effects.
• The result: The screens identify post-Golgi secretory trafficking as central, enabling mechanistic dissection of a common C. albicans aneuploidy and a general framework for studying aneuploidy-linked phenotypes.

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