Characterization of a lipopeptide-resistant strain ofCandida albicans
| Autor: | Amber Shadron, Melinda Knapp, David J. Frost, Kim Brandt, Robert C. Goldman |
|---|---|
| Rok vydání: | 1997 |
| Předmět: |
Antifungal Agents
Ultraviolet Rays Lipoproteins Immunology Mutant Microbial Sensitivity Tests Biology Sensitivity and Specificity Applied Microbiology and Biotechnology Microbiology Mice chemistry.chemical_compound Minimum inhibitory concentration Glycolipid Gene Expression Regulation Fungal Microsomes Candida albicans Genetics medicine Animals Molecular Biology Strain (chemistry) Lipopeptide General Medicine medicine.disease biology.organism_classification Lipids In vitro Biochemistry chemistry Glucosyltransferases Mutagenesis Biological Assay Female Systemic candidiasis |
| Zdroj: | Canadian Journal of Microbiology. 43:122-128 |
| ISSN: | 1480-3275 0008-4166 |
| DOI: | 10.1139/m97-016 |
| Popis: | Lipopeptides are antifungal agents that inhibit cell wall β-(1, 3)-glucan biosynthesis in fungal organisms. A mutant resistant to lipopeptides was generated by UV mutagenesis and characterized. The Candida albicans mutant (LP3-1) was stable and showed resistance specificity to a broad range of lipopeptides and certain glycolipid inhibitors. Other antifungal agents with diverse modes of action had a normal minimum inhibitory concentration profile for LP3-1 compared with the wild-type strain (CCH 442). In the in vitro β-(1, 3)-glucan synthase assay, both the lipopeptides and papulacandin-related agents had considerably higher 50% inhibitory concentration values in the LP3-1 strain than in the wild-type strain. In reconstitution assays, the resistance factor was associated with the integral membrane pellet rather than the peripheral GTP-binding protein. The LP3-1 strain had a membrane lipid profile similar to that of the parent strain and was virulent in a murine model of systemic candidiasis. Taken together, these results indicate that the resistance factor is associated with the integral membrane component of β-(1, 3)-glucan synthase. Lipopeptides are common antifungal agents encountered during screening of natural products. The LP3-1 strain was resistant to natural product extracts known to contain various lipopeptides. Thus, LP3-1 can be used in a dereplication assay.Key words: Candida albicans, β-(1, 3)-glucan synthase, lipopeptides, drug resistance. |
| Databáze: | OpenAIRE |
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