linoleic-acid and Candidiasis

Vulvovaginal candidiasis (VVC) is an inflammatory disease primarily infected by Candida albicans. The condition has good short-term treatment effects, high recurrence, and seriously affects the quality of life of women. Metabolomics has been applied to research a variety of inflammatory diseases. In the present study, the vaginal metabolic profiles of VVC patients and healthy populations (Cnotrol (CTL)) were explored by a non-targeted metabolomics approach. In total, 211 differential metabolites were identified, with the VVC group having 128 over-expressed and 83 under-expressed metabolites compared with healthy individuals. Functional analysis showed that these metabolites were mainly involved in amino acid metabolism and lipid metabolism. In addition, network software analysis indicated that the differential metabolites were associated with mitogen-activated protein kinase (MAPK) signaling and NF-κB signaling. Further molecular docking suggested that linoleic acid can bind to the acyl-CoA synthetase 1 (ACSL1) protein, which has been shown to be associated with multiple inflammatory diseases and is an upstream regulator of the MAPK and NF-κB signaling pathways that mediate inflammation. Therefore, our preliminary analysis results suggest that VVC has a unique metabolic profile. Linoleic acid, a significantly elevated unsaturated fatty acid in the VVC group, may promote VVC development through the ACSL1/MAPK and ACSL1/NF-κB signaling pathways. This study's findings contribute to further exploring the mechanism of VVC infection and providing new perspectives for the treatment of Candida albicans vaginal infection.. Candida albicans is the main pathogen that causes VVC. Through non-targeted metabolomics, this study shows that VVC caused by C. albicans has unique vaginal metabolic characteristics, the changed metabolites might provide useful diagnostic and therapeutic methods for VVC.

Topics: Animals; Antifungal Agents; Candida albicans; Candidiasis; Candidiasis, Vulvovaginal; Female; Homeostasis; Linoleic Acid; Metabolomics; Molecular Docking Simulation; NF-kappa B; Quality of Life

Polyunsaturated fatty acids (PUFAs), including linoleic acid (C18 : 2) and alpha-linolenic acid (C18 : 3), are major components of membranes. PUFAs are produced from monounsaturated fatty acids by several fatty acid desaturases (FADs) in many fungi, but Saccharomyces cerevisiae, Schizosaccharomyces pombe and humans do not have these enzymes. Although the fungal pathogen Candida albicans produces C18 : 2 and C18 : 3, the enzymes that synthesize them have not yet been investigated. In this report, two ORFs, CaFAD2 and CaFAD3, were identified based on their homology to other yeast FADs, and CaFAD2 and CaFAD3 gene disruptants were constructed. Cafad2Delta and Cafad3Delta lost their ability to produce C18 : 2 and C18 : 3, respectively. Furthermore, S. cerevisiae cells expressing CaFad2p converted palmitoleic acid (C16 : 1) and C18 : 1 to hexadecadienoic acid (C16 : 2) and C18 : 2, respectively, and CaFad3p-expressing cells converted C18 : 2 to C18 : 3. These results strongly supported that CaFAD2 encodes the Delta12 FAD and that CaFAD3 encodes the omega3 FAD. However, phenotypic analysis demonstrated that the presence of these PUFAs did not affect the virulence to mice, or morphogenesis in the culture media used to induce morphological change of C. albicans.

Topics: alpha-Linolenic Acid; Amino Acid Sequence; Animals; Candida albicans; Candidiasis; Disease Models, Animal; Fatty Acid Desaturases; Fatty Acids; Fatty Acids, Monounsaturated; Gas Chromatography-Mass Spectrometry; Gene Deletion; Linoleic Acid; Male; Mice; Mice, Inbred ICR; Molecular Sequence Data; Mutagenesis, Insertional; Recombinant Proteins; Saccharomyces cerevisiae; Sequence Homology, Amino Acid; Virulence