A rewired inositol response: Regulation of inositol homeostasis and its contribution to antifungal tolerance in Candida albicans
Year: 2026
Type: dissertation
Abstract: Candida albicans is the most common cause of candidiasis, which includes 1.6 million invasive infections annually, and rising antifungal resistance has narrowed an already limited treatment repertoire. Inositol, acquired through the transporter Itr1p or synthesized de novo by Ino1p, is essential yet understudied as a therapeutic target. Its regulation is well defined in Saccharomyces cerevisiae but not conserved in C. albicans. Transcriptome analysis identified a narrow, temporally staged set of inositol-responsive genes, with only INO1 and ITR1 shared between the two species. A candidate screen implicated two ergosterol biosynthesis genes, ERG251 and ERG26, linking inositol availability to sterol metabolism. ino1-/- strains were susceptible to three antifungal classes even in inositol-replete media, indicating a role for INO1 beyond inositol supply. ITR1 disruption produced drug-specific effects, and antifungal exposure altered inositol gene expression in patterns that differed by drug class. Inositol metabolism therefore represents a potential target for antifungal development.
Author: Sumbler, Erica
Institution: Western University
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7221297795