Project description:We measured protein translation (by ribosome profiling) and RNA levels (by polyA-enriched RNA-seq) in Cryptococcus neoformans strain H99 and Cryptococcus neoformans strain JEC21. This is the first transcriptome-wide map of translation in this species complex.
Project description:Purpose: The purpose of this study is to define the mechanism of antifungal action of the vanillin derivative, o-vanillin, against Cryptococcus neoformans Methods: mRNA profiles of C. neoformasn cells cultured with or without o-vanillin were generated by RNA-Seq, using Illumina GAIIx. The sequence reads that passed quality filters were mapped to reference genome and the normalized RPKM values were calculated by CLC Genomics Workbench. Results: o-vanillin significantly altered global transcript profiles, induces oxidative stress, and interferes mitochondrial functions in C. neoformans. Conclusions: o-vanillin can be considered as the effective antifungal drug candidate.
Project description:Purpose: The purpose of this study is to define the mechanism of antifungal action of the vanillin derivative, o-vanillin, against Cryptococcus neoformans Methods: mRNA profiles of C. neoformasn cells cultured with or without o-vanillin were generated by RNA-Seq, using Illumina GAIIx. The sequence reads that passed quality filters were mapped to reference genome and the normalized RPKM values were calculated by CLC Genomics Workbench. Results: o-vanillin significantly altered global transcript profiles, induces oxidative stress, and interferes mitochondrial functions in C. neoformans. Conclusions: o-vanillin can be considered as the effective antifungal drug candidate. mRNA profiles of the cells grown in the presence or absence of o-vanillin were generated by RNA-Seq using Illumina GAIIx.
Project description:Invasive fungal infections (IFIs) are difficult to treat. Few effective antifungal drugs are available and many have problems with toxicity, efficacy and drug-resistance. To overcome these challenges, existing therapies may be enhanced using more than one agent acting in synergy. Previously, we have found amphotericin B (AMB) and the iron chelator, lactoferrin (LF), were synergistic against Cryptococcus neoformans and Saccharomyces cerevisiae. This study investigates the mechanism of AMB+LF synergy using RNA-seq in Cryptococcus neoformans H99.
Project description:Cryptococcus neoformans is a ubiquitous environmental fungus that can also cause life-threatening infections in immunocompromised individuals. As a competent pathogen, Cryptococcus needs to reprogram its metabolism to adapt the drastic differences between environmental niches and host niches. A well-curated genome-scale metabolic model (GEM) is a powerful tool to facilitate the investigation of the metabolic resilience of an organism Here we reconstructed and validated iCNG99, a GEM for C. neoformans reference strain H99, and evaluated its predictive performance across 43 growth conditions and gene essentiality benchmarks. The model achieved high confidence essential gene prediction (precision = 0.77) and recapitulated pathways targeted by clinically available antifungals. Integration with transcriptomic and metabolomic data enabled iCNG99 to capture condition-specific metabolic adaptations and to identify candidate vulnerabilities in drug tolerance, revealing metabolic adaptations associated with survival within host conditions and drug susceptibility. Together, iCNG99 provides a systems-level computational platform for investigating C. neoformans metabolism and for prioritizing antifungal vulnerabilities.
Project description:Comparison of transcriptional profiles of WT Cryptococcus neoformans (H99) and strain CM126 (pRPL2b-GAT201) which overexpresses the transcription factor GAT201 using a ribosomal protein promoter Keywords: Genetic modification