ArticleAntimicrobial agents and chemotherapy2005
Functional analysis of CaIPT1, a sphingolipid biosynthetic gene involved in multidrug resistance and morphogenesis of Candida albicans.
Article in Antimicrobial agents and chemotherapy, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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45 citing papers in PubMed, 82 citations in OpenAlex.
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- Unique roles of aminophospholipid translocase Drs2p in governing efflux pump activity, ergosterol level, virulence traits, and host-pathogen interaction in Candida albicans.International microbiology : the official journal of the Spanish Society for Microbiology · 2022Article
- Inhibition of Pathogenic Bacteria and Fungi by Natural Phenoxazinone from Octopus Ommochrome Pigments.Journal of microbiology and biotechnology · 2022Article
- Inositol Phosphoryl Transferase, Ipt1, Is a Critical Determinant of Azole Resistance and Virulence Phenotypes inJournal of fungi (Basel, Switzerland) · 2022Article
- Activity ofNanomaterials (Basel, Switzerland) · 2022Article
- Myriocin enhances the antifungal activity of fluconazole by blocking the membrane localization of the efflux pump Cdr1.Frontiers in pharmacology · 2022Article
- Functions of Sphingolipids in Pathogenesis During Host-Pathogen Interactions.Frontiers in microbiology · 2021Review
- Fungal sphingolipids: role in the regulation of virulence and potential as targets for future antifungal therapies.Expert review of anti-infective therapy · 2020Review
- A detailed lipidomic study of human pathogenic fungi Candida auris.FEMS yeast research · 2020Article
- Phospholipid biosynthesis disruption renders the yeast cells sensitive to antifungals.Folia microbiologica · 2020Article
- Linking Cellular Morphogenesis with Antifungal Treatment and Susceptibility inJournal of fungi (Basel, Switzerland) · 2019Review
- Candida albicans gains azole resistance by altering sphingolipid composition.Nature communications · 2018Article
- The Rim Pathway Mediates Antifungal Tolerance in Candida albicans through Newly Identified Rim101 Transcriptional Targets, Including Hsp90 and Ipt1.Antimicrobial agents and chemotherapy · 2018Article
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In the present study we describe the isolation and functional analysis of a sphingolipid biosynthetic gene, IPT1, of Candida albicans. The functional consequence of the disruption of both alleles of IPT1 was confirmed by mass analysis of its sphingolipid composition. The disruption of both alleles or a single allele of IPT1 did not lead to any change in growth phenotype or total sphingolipid, ergosterol, or phospholipid content of the mutant cells. The loss of mannosyl diinositol diphosphoceramide [M(IP)(2)C] in the ipt1 disruptant, however, resulted in increased sensitivity to drugs like 4-nitroquinoline oxide, terbinafine, o-phenanthroline, fluconazole, itraconazole, and ketoconazole. The increase in drug susceptibilities of ipt1 cells was linked to an altered sphingolipid composition, which appeared to be due to the impaired functionality of Cdr1p, a major drug efflux pump of C. albicans that belongs to the ATP binding cassette superfamily. Our confocal and Western blotting results demonstrated that surface localization of green fluorescent protein-tagged Cdr1p was affected in ipt1 disruptant cells. Poor surface localization of Cdr1p resulted in an impaired ability to efflux fluconazole and rhodamine 6G. The effect of mannosyl inositol phosphoceramide accumulation in the ipt1 mutant and the absence of M(IP)(2)C from the ipt1 mutant on the efflux of drug substrates was very selective. The efflux of methotrexate, a specific substrate of CaMdr1p, another major efflux pump of major facilitator superfamily, remained unaffected in ipt1 mutant cells. Interestingly, changes in sphingolipid composition affected the ability of mutant cells to form proper hyphae in various media. Taken together, our results demonstrate that an altered composition of sphingolipid, which is among the major constituents of membrane rafts, affects the drug susceptibilities and morphogenesis of C. albicans.
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