Acetylcholine Induces Yeast to Hyphal Form Transition in Candida albicans

Ali, Awad; Karuppayil, Sankunny Mohan

doi:10.4172/2165-8056.1000154

Cited by 3 publications

References 36 publications

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Integrative functional analysis uncovers metabolic differences between Candida species

et al. 2022

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Candida species are a dominant constituent of the human mycobiome and associated with the development of several diseases. Understanding the Candida species metabolism could provide key insights into their ability to cause pathogenesis. Here, we have developed the BioFung database, providing an efficient annotation of protein-encoding genes. Along, with BioFung, using carbohydrate-active enzyme (CAZymes) analysis, we have uncovered core and accessory features across Candida species demonstrating plasticity, adaption to the environment and acquired features. We show a greater importance of amino acid metabolism, as functional analysis revealed that all Candida species can employ amino acid metabolism. However, metabolomics revealed that only a specific cluster of species (AGAu species—C. albicans, C. glabrata and C. auris) utilised amino acid metabolism including arginine, cysteine, and methionine metabolism potentially improving their competitive fitness in pathogenesis. We further identified critical metabolic pathways in the AGAu cluster with biomarkers and anti-fungal target potential in the CAZyme profile, polyamine, choline and fatty acid biosynthesis pathways. This study, combining genomic analysis, and validation with gene expression and metabolomics, highlights the metabolic diversity with AGAu species that underlies their remarkable ability to dominate they mycobiome and cause disease.

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Integrative functional analysis uncovers metabolic differences between Candida species

et al. 2022

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Integrative functional analysis uncovers metabolic differences between Candida species

Begum

Lee

Pellón

et al. 2021

Preprint

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Candida species are a dominant constituent of the human mycobiome and a better understanding of their metabolism from a fungal perspective can provide key insights into their ability to cause pathogenesis. Here, we have developed the BioFung database a fungal specific tool for functional annotation using the KEGG database that provides an efficient method for annotation of protein-encoding gene. Analysis of carbohydrate-active enzyme (CAZymes) and BioFung, uncovered core and accessory features across Candida species demonstrating plasticity, adaptation to the environment and acquired features. Integerative functional analysis revealed that all Candida species can employ amino acid metabolism. However, metabolomics revealed that only a specific cluster of species (AGAu species; C. albicans, C. glabrata and C. auris) utilised amino acid metabolism. We identified critical metabolic pathways in the AGAu clusters with biomarkers and antifungal target potential in the CAZyme profile, polyamine, choline and fatty acid biosynthesis pathways. This study, combining genomic analysis, metabolomics and gene expression validation, highlights the metabolic diversity within AGAu species that underlies their remarkable ability to dominate the mycobiome and cause disease.

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Candida and Long Covid

Chambers

2024

Preprint

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The pandemic has supercharged growing awareness of the gut microbiome as a critical determinant of human health. Long haulers share microbiomes similar to those seen in myalgic encephalomyelitis/chronic fatigue syndrome and fibromyalgia, all frequently associated with Candida overgrowth (CO). Candida has a unique relationship with IDO and altered tryptophan metabolism (ATM), mediated by IFN-γ. Zonulin, a circulating protein that increases intestinal and endothelial permeability, has emerged as a central player. This protein can be activated by proteases secreted by Candida and mast cells, enabling myriad autoimmune and other chronic diseases. Many of these are seen in long Covid (LC). Candida hyphal walls express proteins that are analogous to gliadin/gluten (celiac disease antibodies) or that are GPCRs, e.g., Crohn’s disease antibodies present only in eukaryotes, that may trigger antigliadin and anti-GPCR autoantibodies respectively. These latter include the Saccharomyces/Candida hyphal GPCR seen in CrD and the Candida hyphal Rrp9 muscarinic GPCR seen in POTS. These two autoantibody producing pathways both activate zonulin and may encompass the broad spectrum of autoimmune diseases seen in LC. IFN-γ, a marker for LC, can activate not only IDO but also zonulin. The spike protein S on SARS CoV2 can attach to both the ACE2 receptor (required for tryptophan absorption) and Toll-like receptor4 (TLR4) bearing cells (endothelial cells and enterocytes). Spike protein S is persistent in LC and, as a ligand for TLR4, can also activate zonulin. S can also activate the nucleotide-binding domain, leucine-rich repeat, and pyrin domain-containing protein 3 (NLRP3) inflammasome, as can candidalysin. This inflammasome is directly connected to dementia, cancer, autoimmunity and obesity. A hypothetical pathophysiologic model is proposed implicating pre-existing CO, aggravated by Covid-19, in not only the genesis of LC but also that of autoimmune disease, dementia, cancer, many chronic diseases, and aging. Candida may accomplish this directly or through IFN-γ induced upregulation of both IDO and zonulin.

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Acetylcholine Induces Yeast to Hyphal Form Transition in Candida albicans

Cited by 3 publications

References 36 publications

Integrative functional analysis uncovers metabolic differences between Candida species

Integrative functional analysis uncovers metabolic differences between Candida species

Integrative functional analysis uncovers metabolic differences between Candida species

Candida and Long Covid

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