title: Candida albicans RHO1 is required for cell viability in vitro and in vivo.
abstract: In Saccharomyces cerevisiae, Rho1p plays an important role in cell wall integrity by regulating beta-1,3-glucan synthase, Pkc1p and the actin cytoskeleton. To determine the physiological role of Rho1p in the dimorphic fungus Candida albicans, the major human fungal pathogen, we constructed mutants that conditionally express Rho1p from the glucose-repressible phosphoenolpyruvate carboxykinase promoter (pPCK1). We examined the growth of these cells in a range of conditions. Depletion of Rho1p from yeast cells resulted in cell death, lysis, and aggregation. The Rho1p conditional mutant was inviable on 10% serum indicating that Rho1p was also required for hyphal viability. Furthermore, in a mouse model of systemic candidiasis, strains dependent on pPCK1-driven RHO1 expression failed to colonise the kidneys and establish disease, suggesting that the level of glucose in serum was sufficient to repress the pPCK1 and that Rho1p-depleted strains were inviable within the host. Therefore, Rho1p is essential for the viability of C. albicans in vitro and in vivo.
authors.affiliation: GPC-biotech Inc., 610 Lincoln Street, Waltham, MA 02451, USA.
authors.forename: Susan E
authors.initials: SE
authors.lastname: Smith
authors.forename: Csilla
authors.initials: C
authors.lastname: Csank
authors.forename: Guadalupe
authors.initials: G
authors.lastname: Reyes
authors.forename: Mahmoud A
authors.initials: MA
authors.lastname: Ghannoum
authors.forename: Vivian
authors.initials: V
authors.lastname: Berlin
mesh_terms: D000818:Animals; D002176:Candida albicans / Q000235:genetics / Q000254:growth & development*; D002470:Cell Survival; D002473:Cell Wall / Q000737:chemistry / Q000378:metabolism*; D003001:Cloning, Molecular; D019204:GTP-Binding Proteins / Q000502:physiology; D066298:In Vitro Techniques; D051379:Mice; D023421:Models, Animal; D010641:Phenotype; D020741:rho GTP-Binding Proteins / Q000502:physiology*
chemical_list: D019204:GTP-Binding Proteins; D020741:rho GTP-Binding Proteins