A novel compound exhibits potent anti-Candida albicans activity
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ABSTRACT:
PROVIDER: PRJNA1213729 | ENA |
REPOSITORIES: ENA
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Project description:Candida albicans is a prevalent fungal pathogen in humans worldwide, causing life-threatening invasive candidiasis in immunocompromised individuals, largely due to the scarcity and poor efficacy of present antifungals, necessitating the search for novel antifungal medications.By leveraging machine learning methodologies, we have identified a novel compound that demonstrates robust antifungal activity against C. albicans. To explore the mechanisms behind its efficacy, we undertook an extensive study involving transcriptomic profiling of C. albicansexposed to the compound across different cultivation times and doses.The findings of this study not only contribute to our understanding of antifungal mechanisms, but also have great potential to guide the development of innovative therapies against C. albicans for meeting the growing clinical demand for new treatments.
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Project description:Candida albicans exhibits distinct cytoprotective responses to anti-fungal drugs
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Project description:6-Nonadecynoic acid (6-NDA), a plant-derived acetylenic acid, exhibits strong inhibitory activity against the human fungal pathogens Candida albicans, Aspergillus fumigatus, and Trichophyton mentagrophytes. In the present study, transcriptional profiling coupled with mutant and biochemical analyses were conducted using the model organism Saccharomyces cerevisiae to investigate the mechanism of action of this compound. 6-NDA elicited a transcriptome response indicative of fatty acid stress, altering the expression of genes known to be affected when yeast cells are grown in the presence of oleate. Mutants of S. cerevisiae lacking transcription factors that regulate fatty acid beta-oxidation showed increased sensitivity to 6-NDA. Fatty acid profile analysis indicated that 6-NDA inhibited the formation of fatty acids longer than 14 carbons in length. In addition, the growth inhibitory effect of 6-NDA was rescued in the presence of exogenously supplied oleate. To investigate the response of a pathogenic fungal species to 6-NDA, transcriptional profiling and biochemical analyses were also conducted in C. albicans. The transcriptional response and fatty acid profile of C. albicans were comparable to those obtained in S. cerevisiae, and the rescue of growth inhibition with exogenous oleate was also observed in C. albicans. In addition, 6-NDA enhanced the potency of the antifungal drug fluconazole in a fluconazole-resistant clinical isolate of C. albicans. Collectively, our results indicate that the antifungal activity of 6-NDA is mediated by a disruption in fatty acid homeostasis, and that this compound has potential utility in combination therapy in the treatment of drug-resistant fungal infections.
2012-02-08 | GSE35604 | GEO
Project description:Candida albicans is the most prevalent human pathogenic fungus, responsible for drug-resistant and fatal invasive infections which show an increasing trend in the past two decades. A promising new therapeutic approach involves NFAP2, an antifungal protein secreted by Neosartorya (Aspergillus) fischeri. NFAP2 exhibits potent antifungal activity on both planktonic and biofilm-forming Candida cells in vitro and in vivo. Despite this promising feature,the exact antifungal mechanism of NFAP2 remains in the shadow which hampers its therapeutic application. Based on our recent observations, we suppose that NFAP2 is taken up by Candida cells, and has a long-term growth-slowing effect. Our objective was to understand the molecular mechanism of the long-term growth slowing effect of NFAP2 in C. albicans, therefore the transcriptome of the NFAP2-treated (below the minimum inhibitory concentration) C. albicans SC5314 cultures was compared to that of the untreated ones.The transcriptional responses to NFAP2 were further characterized using functional enrichment analyses of Gene Ontology terms and Kyoto Encyclopedia of Genes and Genomes pathways.
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