The transcription factor CgHaa1 plays a role in virulence of the pathogenic yeast Candida glabrata.

Abstract

Candida glabrata is a prominent causative agent of mucosal and disseminated human infections. Part of the success of C. glabrata as a human pathogen relies on its adherence capacity and ability to tolerate/surpass the activity of immune cells. Herein we describe the involvement of the transcription factor CgHaa1 and of its regulated genes CgAWP12, CgAWP13, CAGL0H07469 g and CAGL0K10164 g in adherence of C. glabrata to vaginal cells in the presence of acetic acid, an organic acid usually found in this niche due to the activity of commensal bacteria. CgHaa1 and its target genes CgAWP12, CAGL0K10164 g and CAGL0E03740 g were also found to significantly increase C. glabrata-induced killing of the model wax moth Galleria mellonela, in part by modulating the interaction of the yeasts with the larvae's immune cells. Finally, we show that CgHAA1 expression reduces ingestion and subsequent killing of C. glabrata cells by THP-1 human macrophages. This demonstrated role of CgHaa1 in C. glabrata virulence and interaction with immune cells expands the biological role of this regulator positioning it (and its target genes) as a potential interesting candidate target for new therapies focused on reducing the burden of candidiasis.