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      Fluconazole and amphotericin-B resistance are associated with increased catalase and superoxide dismutase activity in Candida albicans and Candida dubliniensis

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          Abstract

          Introduction Candida dubliniensis, a new species of Candida that has been recovered from several sites in healthy people, has been associated with recurrent episodes of oral candidiasis in AIDS and HIV-positive patients. This species is closely related to C. albicans. The enzymatic activity of C. dubliniensis in response to oxidative stress is of interest for the development of drugs to combat C. dubliniensis. Methods Fluconazole- and amphotericin B-resistant strains were generated as described by Fekete-Forgács et al. (2000). Superoxide dismutase (SOD) and catalase assays were performed as described by McCord and Fridovich (1969) and Aebi (1984), respectively. Results We demonstrated that superoxide dismutase (SOD) and catalase activities were significantly higher (p<0.05) in the fluconazole- and amphotericin B-resistant strains of C. dubliniensis and C. albicans than in the sensitive strains. The catalase and SOD activities were also significantly (p<0.01) higher in the sensitive and resistant C. albicans strains than in the respective C. dubliniensis strains. Conclusions These data suggest that C. albicans is better protected from oxidative stress than C. dubliniensis and that fluconazole, like amphotericin B, can induce oxidative stress in Candida; oxidative stress induces an adaptive response that results in a coordinated increase in catalase and SOD activities.

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          Most cited references34

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          Azole antifungal agents.

          G Bodey (1992)
          The discovery of the antifungal activity of azole compounds represented an important therapeutic advance. Miconazole, ketoconazole, and fluconazole are currently commercially available, and itraconazole has undergone extensive clinical evaluation. Because of its limited activity and toxicity, miconazole has been replaced by newer agents. Ketoconazole has proven useful in therapy for superficial infections and invasive infections caused by the pathogenic fungi. Among its disadvantages are limited absorption in the absence of gastric acid and its potential for drug-drug interactions. Fluconazole is the only azole available as oral and intravenous preparations. Unlike other azoles, it is only minimally metabolized in the liver and largely excreted in the urine as active drug. It is more effective than ketoconazole against superficial candidal infections and is the drug of choice for maintenance therapy for cryptococcal meningitis in patients infected with human immunodeficiency virus. An advantage of itraconazole is its activity against aspergillosis. It is also active against many infections caused by pathogenic fungi. Other azole compounds are at varying stages of preclinical and clinical investigation.
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            Catalase gene disruptant of the human pathogenic yeast Candida albicans is defective in hyphal growth, and a catalase-specific inhibitor can suppress hyphal growth of wild-type cells.

            Y Nakagawa (2007)
            Although the catalase gene (CAT1) disruptant of the human pathogenic yeast Candida albicans was viable under ordinary growth conditions, we previously found that it could not grow on YPD (yeast extract/peptone/dextrose) containing SDS or at higher growth temperatures. To investigate the pleiotrophic nature of the disruptant, we examined the effect of the catalase inhibitor 3-AT on the growth of wild-type strains. Surprisingly, the addition of 3-AT and SDS caused the wild-type cells to be non-viable on YPD plates. We found an additional phenotype of the catalase gene disruptant: it did not produce normal hyphae on Spider medium. Hyphal growth was observed in a CAP1 (Candida AP-1-like protein gene) disruptant, a HOG1 (high-osmolarity glycerol signaling pathway gene) disruptant, and the double CAP1/HOG1 disruptant, suggesting that the defect in hyphal formation by the catalase disruptant was independent of these genes. Addition of 3-AT and SDS to hyphae-inducing media suppressed growth of normal hyphae in the wild-type strain. The potential necessity for catalase action upon exposure to hyphae-inducing conditions was confirmed by the immediate elevation of the catalase gene message. In spite of the requirement for catalase during hyphal growth, the catalase gene disruptant was capable of forming germ tubes in medium containing serum.
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              Suggested mechanisms for the antimycotic activity of the polyene antibiotics and the N-substituted imidazoles.

              A Thomas (1986)
              The polyene antibiotics and the N-substituted imidazoles (azoles) are two groups of clinically important antifungal drugs. Both are hydrophobic and both interact with the plasma membrane of susceptible fungi but the mode of action of the two groups is not fully resolved. In this paper their biological properties are reviewed in the context of recent work so that common features may be identified and further areas of research indicated.
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                Author and article information

                Contributors
                Role: ND
                Role: ND
                Role: ND
                Role: ND
                Role: ND
                Role: ND
                Journal
                rsbmt
                Revista da Sociedade Brasileira de Medicina Tropical
                Rev. Soc. Bras. Med. Trop.
                Sociedade Brasileira de Medicina Tropical - SBMT (Uberaba )
                1678-9849
                December 2013
                : 46
                : 6
                : 752-758
                Affiliations
                [1 ] Universidade Federal do Rio Grande do Sul Brazil
                [2 ] Universidade Regional Integrada do Alto do Uruguai e das Missões Brazil
                [3 ] Universidade Federal de Santa Maria Brazil
                [4 ] Universidade Federal de Santa Maria Brazil
                Article
                S0037-86822013000600752
                10.1590/0037-8682-0190-2013
                24474018
                a5cb24bd-9481-4dc3-8ad4-d5619514f110

                http://creativecommons.org/licenses/by/4.0/

                History
                Product

                SciELO Brazil

                Self URI (journal page): http://www.scielo.br/scielo.php?script=sci_serial&pid=0037-8682&lng=en
                Categories
                TROPICAL MEDICINE

                Infectious disease & Microbiology
                Catalase,Superoxide dismutase,Candida albicans,Candida dubliniensis

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