Study Info
INDA Accessions: INRP000485
INSDC Accessions: PRJEB100851, ERP182297
- Title: Discovery of a Lithocholic Acid-Imidazolium Targeting C18 Ceramide Synthase as a Potential Antifungal against Candida Infections
- Data Type : RNASeq
- Descriptive Title: Fungal Infections, Sphingolipid Metabolism, Membrane Homeostasis, Lithocholic Acid
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Organism:
Scientific Name(Taxon Id): Candida albicans (5476) Common Name:
Other Info
- Abstract: Candida albicans is a commensal and opportunistic pathogen associated with oral, vaginal, cutaneous, and invasive candidiasis predominantly in immunodeficient individuals. We report the synthesis and screening of a chemical library based on different bile acid scaffolds against C. albicans. We identified an imidazolium derivative of lithocholic acid as an effective antifungal that is also effective against various Candida species, including C. albicans and Candidozyma auris clinical isolates. RNA sequencing and lipidomics studies revealed that 22 alters the sphingolipid metabolism in C. albicans, diminishes C18 ceramides, and enhances the accumulation of toxic lipids like phytosphingosine and dihydrosphingosine. Further screening and validation studies using mutant strains validated that 22 interacts with C18 chain specific ceramide synthase through three key amino acid residues W193, M212, and H216. These alterations in lipids cause membrane- associated ER stress, mitochondrial toxicity, and reactive oxygen species, which are responsible for cell death. Finally, we demonstrated that the liposomal formulation of 22 can inhibit the fungal load in the murine systemic candidiasis model without causing any toxicity. Therefore, targeting sphingolipid metabolism in C. albicans using lithocholic acid-imidazolium offers a promising platform to address the challenges with fungal infections, including multidrug resistance.
- Linked publications:
- Center Name: Avinash Bajaj, Regional Centre for Biotechnology, India
- Number of Base(Total) Mbp: 56,450,571,423
- Size in bytes(Total): 34,367,800,602
- Number of sample:
- Number of Runs:
- Number of Sequences:
- Number of Assembly:
- Number of Variant files:
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