The genotoxic stress-inducible gene GEI1(Orf19.3109) is a repressor of virulence in Candida albicans

While many DNA damage response (DDR) genes are well-characterized, the functions of pathogen-specific, stress-inducible genes remain enigmatic. Here, we characterized GEI1 (Orf19.3109), a gene robustly induced by genotoxic agents and oxidative stress, which lacks a discernible ortholog in Saccharomyces cerevisiae.

Unexpectedly, although GEI1 expression is triggered by DNA damage, its deletion does not impair genotoxin tolerance. Instead, the gei1Δ/Δ mutant exhibits a striking increase in resistance to oxidative stress, characterized by reduced intracellular reactive oxygen species (ROS) accumulation and attenuated apoptosis. Furthermore, loss of GEI1 leads to massive hyper-secretion of extracellular aspartyl proteases (Saps) and displays an extreme hypervirulence phenotype in the Galleria mellonella infection model.