oligomycins and Candidiasis

In this study, 18 predicted membrane-localized ABC transporters of Candida glabrata were deleted individually to create a minilibrary of knockouts (KO). The transporter KOs were analyzed for their susceptibility toward antimycotic drugs. Although Cg

Topics: Antifungal Agents; ATP-Binding Cassette Transporters; Azoles; Calcineurin; Candida glabrata; Candidiasis; Drug Resistance, Fungal; Fluconazole; Fungal Proteins; Membrane Transport Proteins; Microbial Sensitivity Tests; Nitrogen; Oligomycins; Sirolimus

Signal transduction pathways mediated by mitogen-activated protein kinases (MAPKs) play crucial roles in eukaryotic cells. In the pathogenic fungus Candida albicans the HOG MAPK pathway regulates the response to external stresses (osmotic and oxidative among others) and is involved in morphogenesis and virulence. We show here that the lack of the Hog1 MAPK increases the sensitivity of this fungus to inhibitors of the respiratory chain. hog1 mutants also show an enhanced basal respiratory rate compared to parental strains, and higher levels of intracellular reactive oxygen species despite an increased expression of detoxifying enzymes. We also demonstrate that although oxidative phosphorylation is essentially unaffected, hog1 mutants have an altered mitochondrial membrane potential. Data indicate that hog1-defective mutants are more dependent on mitochondrial ATP synthesis, probably due to an increased cellular ATP demand. Our results therefore link a MAPK pathway with respiratory metabolism in pathogenic fungi.

Topics: Adenosine Triphosphate; Candida albicans; Candidiasis; Chloramphenicol; Electron Transport; Fungal Proteins; Membrane Potential, Mitochondrial; Mitochondria; Mitogen-Activated Protein Kinases; Mutation; Oligomycins; Oxidative Stress; Oxygen