Candida albicans virulence and drug-resistance requires the O-acyltransferase Gup1p

Abstract

Background GUP1 gene was primarily identified in Saccharomyces cerevisiae being connected with glycerol uptake defects in association with osmotic stress response. Soon after, Gup1p was implicated in a complex and extensive series of phenotypes involving major cellular processes. These include membrane and wall maintenance, lipid composition, bud-site selection, cytoskeleton orientation, vacuole morphology, secretory/endocytic pathway, GPI anchors remodelling and lipid-ordered domains assembly, which is compatible with their inclusion in the Membrane Bound O-acyl transferases (MBOAT) family. In mammals, it has been described as a negative regulator of the Sonic hedgehog pathway, involved in morphogenesis, differentiation, proliferation, among other processes.

Results We show that Candida albicans Gup1p strongly interferes with the capacity of cells to develop hyphae, to adhere, to invade and to form a biofilm, all of which are significant virulence factors. Furthermore, the mutant colonies exhibited an aberrant morphology/differentiation pattern. Identically to S. cerevisiae, Cagup1delta null mutant was more resistant to antifungals like fluconazole, ketoconazole and clotrimazole and displayed an abnormal even sterol distribution at the plasma membrane.

Conclusions This work is the first study in the opportunistic yeast Candida albicans, showing a role for the GUP1 gene in virulence as well as in the mechanisms underlying antifungal resistance. However, its impact is even more significant since, these results taken together with all the knowledge about GUP1 gene (from S. cerevisiae and mammals) give consistence to the possibility that Gup1p may be part of a yeast morphogenic pathway parallel to the mammalian Hedgehog.