ubiquinone and Candidiasis

Topics: Antifungal Agents; Candidiasis; Chlorophyta; Cryptococcosis; DNA; Humans; Mycoses; Ubiquinone; Yeasts

The fungal pathogen Candida albicans causes lethal systemic infections in humans. To better define how pathogens resist oxidative attack by the immune system, we examined a family of four Flavodoxin-Like Proteins (FLPs) in C. albicans. In agreement with previous studies showing that FLPs in bacteria and plants act as NAD(P)H quinone oxidoreductases, a C. albicans quadruple mutant lacking all four FLPs (pst1Δ, pst2Δ, pst3Δ, ycp4Δ) was more sensitive to benzoquinone. Interestingly, the quadruple mutant was also more sensitive to a variety of oxidants. Quinone reductase activity confers important antioxidant effects because resistance to oxidation was restored in the quadruple mutant by expressing either Escherichia coli wrbA or mammalian NQO1, two distinct types of quinone reductases. FLPs were detected at the plasma membrane in C. albicans, and the quadruple mutant was more sensitive to linolenic acid, a polyunsaturated fatty acid that can auto-oxidize and promote lipid peroxidation. These observations suggested that FLPs reduce ubiquinone (coenzyme Q), enabling it to serve as an antioxidant in the membrane. In support of this, a C. albicans coq3Δ mutant that fails to synthesize ubiquinone was also highly sensitive to oxidative stress. FLPs are critical for survival in the host, as the quadruple mutant was avirulent in a mouse model of systemic candidiasis under conditions where infection with wild type C. albicans was lethal. The quadruple mutant cells initially grew well in kidneys, the major site of C. albicans growth in mice, but then declined after the influx of neutrophils and by day 4 post-infection 33% of the mice cleared the infection. Thus, FLPs and ubiquinone are important new antioxidant mechanisms that are critical for fungal virulence. The potential of FLPs as novel targets for antifungal therapy is further underscored by their absence in mammalian cells.

Topics: Animals; Candida albicans; Candidiasis; Cells, Cultured; Female; Flavodoxin; Flavoproteins; Fungal Proteins; Gene Deletion; Immune Evasion; Isoenzymes; Macrophages; Mice, Inbred BALB C; Microbial Viability; NADH, NADPH Oxidoreductases; Oxidation-Reduction; Oxidative Stress; Substrate Specificity; Ubiquinone; Virulence

Candida dubliniensis is a newly recognized species closely phylogenetically related to Candida albicans and is commonly associated with oral candidiasis in human immunodeficiency virus-positive patients. In this paper we report the isolation of three strains of C. dubliniensis, from AIDS patients, in the state of Rio Grande do Sul (Brazil). The phenotypic identification was based on germ tube emission, abundant production of chlamydospores, assimilation of sucrose but not of xylose and the inability to grow at 42 degrees C. Randomly amplified polymorphic DNA (RAPD) analysis and genomic DNA sequencing confirmed the distinct genetic nature C. dubliniensis. Topics related to the epidemiology, isolation, phenotypical and genotypical identification of C. dubliniensis are also discussed.

Topics: Adult; AIDS-Related Opportunistic Infections; Candida; Candidiasis; Culture Media; DNA, Fungal; Female; Genotype; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Phenotype; Random Amplified Polymorphic DNA Technique; Spores, Fungal; Sucrose; Ubiquinone; Xylose

Some Candida species which were similar to each other in phenotypic characteristics were studied by chemotaxonomic and molecular taxonomic comparison including the ubiquinone systems, electrophoretic karyotypes, DNA base composition and DNA relatedness. Candida viswanathii and Candida lodderae showed similar electrophoretic karyotypes and DNA base composition and demonstrated 89 to 91% DNA relatedness, confirming their synonymy.

Topics: Base Composition; Candida; Candidiasis; Cerebrospinal Fluid; DNA, Fungal; Electrophoresis, Gel, Pulsed-Field; Food Microbiology; Humans; Karyotyping; Nucleic Acid Hybridization; Phenotype; Sputum; Ubiquinone