Deletion of Increases Antifungal Drug Susceptibility and Virulence in Candida glabrata.

, the second most frequent cause of candidiasis after , is an emerging human fungal pathogen that is intrinsically drug tolerant. Currently, studies of genes involved in drug tolerance are limited. Ada2, a component serving as a transcription adaptor of the Spt-Ada-Gcn5 acetyltransferase (SAGA) complex, is required for antifungal drug tolerance and virulence in However, its roles in remain elusive. In this study, we found that mutants demonstrated severe growth defects at 40°C but only mild defects at 37°C or 25°C. In addition, mutants exhibited pleiotropic phenotypes, including susceptibility to three classes of antifungal drugs (i.e., azoles, echinocandins, and polyenes) and cell wall-perturbing agents but resistance to the endoplasmic reticulum stressor tunicamycin. According to RNA sequence analysis, the expression of 43 genes was downregulated and the expression of 442 genes was upregulated in the mutant compared to their expression in the wild type. , along with its downstream target , controls antifungal drug tolerance and cell wall integrity. Surprisingly, mutants were hypervirulent in a murine model of systemic infection, possibly due to the upregulation of multiple adhesin-like genes, increased agar invasion, and overstimulation of murine tumor necrosis factor alpha production.