Comprehensive genome-scale metabolic model of the human pathogen Cryptococcus neoformans : A platform for understanding pathogen metabolism and identifying new drug targets

• Published in: Frontiers in bioinformatics 2023, Vol.3, p.1121409-1121409
• Main Authors: Tezcan, Enes Fahri, Demirtas, Yigit, Cakar, Zeynep Petek, Ulgen, Kutlu O
• Format: Article
• Language: English
• Subjects: Bioinformatics; cryptococcus neoformans; drug target; gene essentiality; genome scale metabolic model; metabolic reconstruction
• ISSN: 2673-7647; 2673-7647
• DOI: 10.3389/fbinf.2023.1121409

The fungal priority pathogen causes cryptococcal meningoencephalitis in immunocompromised individuals and leads to hundreds of thousands of deaths per year. The undesirable side effects of existing treatments, the need for long application times to prevent the disease from recurring, the lack of resources for these treatment methods to spread over all continents necessitate the search for new treatment methods. Genome-scale models have been shown to be valuable in studying the metabolism of many organisms. Here we present the first genome-scale metabolic model for , iCryptococcus. This comprehensive model consists of 1,270 reactions, 1,143 metabolites, 649 genes, and eight compartments. The model was validated, proving accurate when predicting the capability of utilizing different carbon and nitrogen sources and growth rate in comparison to experimental data. The compatibility of the Cryptococcus metabolism under infection conditions was assessed. The steroid and amino acid metabolisms found in the essentiality analyses have the potential to be drug targets for the therapeutic strategies to be developed against Cryptococcus species. iCryptococcus model can be applied to explore new targets for antifungal drugs along with essential gene, metabolite and reaction analyses and provides a promising platform for elucidation of pathogen metabolism.