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The transcription factor Pdr802 regulates Titan cell production and Cryptococcus neoformans pathogenicity

ABSTRACT: The transcription factor Pdr802 regulates Titan cell production and Cryptococcus neoformans pathogenicity

PROVIDER: PRJNA641574 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR12081264_1.fastq.gz	Fastqsanger.gz
	SRR12081264_2.fastq.gz	Fastqsanger.gz
	SRR12081265_1.fastq.gz	Fastqsanger.gz
	SRR12081265_2.fastq.gz	Fastqsanger.gz
	SRR12081266_1.fastq.gz	Fastqsanger.gz

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The transcription factor Pdr802 regulates Titan cell production and Cryptococcus neoformans pathogenicity

Project description:We report on our study the role of C. neoformans transcription factor Pdr802, whose expression is highly induced under host-like conditions in vitro and is critical for C. neoformans dissemination and virulence in a mouse model of infection. We found that direct targets of Pdr802 include the calcineurin targets Had1 and Pmc1, which are important for C. neoformans virulence, the transcription factor Bzp4, which promotes cryptococcal melanization and capsule thickness, and 35 transmembrane transporters. Notably, a strain engineered to lack Pdr802 showed a dramatically increased population of Titan cells. Since Titan cells are not phagocyted and do not disseminate via the Trojan horse mechanism or via penetration of biological barriers, this likely explains the reduced dissemination of pdr802 cells to the central nervous system and consequently reduced pathogenicity of this strain. The role of Pdr802 as a negative regulator of titanisation is thus critical for cryptococcal virulence.

2021-02-16 | GSE153134 | GEO

The transcription factor Pdr802 regulates Titan cell production and Cryptococcus neoformans pathogenicity (RNA-Seq)

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The transcription factor Pdr802 regulates Titan cell production and Cryptococcus neoformans pathogenicity (RNA-Seq)

Project description:The transcription factor Pdr802 regulates Titan cell production and Cryptococcus neoformans pathogenicity (RNA-Seq)

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Global proteomic analysis in Cryptococcus neoformans

Project description:Discovering the Roles of the Casein Kinase 2 Complex in the Growth, Differentiation, Stress Responses, and Pathogenicity of Cryptococcus neoformans

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Unraveling the Mechanism of Thermotolerance in Cryptococcus neoformans by Set3C Complex

Project description:Thermotolerance, a key factor essential for the virulence of pathogenic fungi including Cryptococcus neoformans, remains largely unexplored in terms of its underlying mechanism. In this study, our findings demonstrate that Set3C, a widely distributed and conserved histone deacetylase complex, is required for thermotolerance in Cryptococcus neoformans. Specifically, the deletion of the core subunit Set302, responsible for the integrity of the complex, results in a significant reduction in the growth ability under high stress and the viability at extreme temperature. Moreover, the absence of Set302 leads to a decrease in the production of capsule and melanin. Transcriptomics analysis revealed that Set302 regulates a large number of genes compared to normal condition, and their expression is responsive to heat stress. Notably, we observed that Set302 positively influences the expression of genes related to ubiquitin-proteasome system (UPS) at high temperature. Using GFP-α-synuclein overexpression model, we observed a pronounced accumulation of misfolded proteins under heat stress, consequently inhibiting the thermotolerance of Cryptococcus neoformans. Furthermore, the loss of Set302 exacerbates this inhibition of thermotolerance. Interestingly, set302∆ strain exhibits a similar phenotype under proteasome stress as it does under high temperature. We also found that set302∆ strain displayed significantly reduced pathogenicity and colonization ability compared to the wild-type strain in the murine infection model. Collectively, our findings indicate that Set302 modulates the degradation of misfolded proteins through the UPS pathway, thereby affecting the thermotolerance and pathogenicity of Cryptococcus neoformans.

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Ribosome profiling of Cryptococcus neoformans H99

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.

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CoCl2 Response in Cryptococcus neoformans

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Differentiated protein extracts from freshwater and terrestrial mollusks inhibit virulence factor production in Cryptococcus neoformans

Project description:Cryptococcus neoformans is a fungal pathogen responsible for an increased mortality among immunocompromised individuals. Long antifungal therapies to treat cryptococcal infections have compounded the occurrence of resistant strains that threaten the efficacy of current treatments. In this senseDue to resistance mechanisms, discovery of compounds that inhibit virulence factors, rather than kill the fungus, have emerged as potential new strategies to combat infection and reduce the rate of resistance due to lower selective pressure. Invertebrates rely solely on an effective innate immune system to prevent infections, provide providing a potential one health approach for discovery of novel antifungal and antibacterial compounds. Here, we demonstrate a differentiated extraction of proteins from three mollusks (freshwater and terrestrial) and evaluate extract their effects against the growth and virulence factor production (thermotolerance, melanin, capsule, and biofilm) in C. neoformans. We show that clarified extracts of Planorbella pilsbryi have a fungicidal effect on cryptococcal cells in a comparable way to Fluconazolefluconazole. Similarly, crude and clarifiedall extracts of Cipangopaludina chinensis not only affects cryptococcal thermotolerance but also impairs biofilm and capsule production. In addition, incubation of C. neoformans with clarified extracts of Cepaea nemoralis extracts reduced capsule production. Using inhibitory activity of extracts against peptidases related with virulence factors and Quantitative quantitative proteomics arose distinct proteome signatures for each extract and proposed proteins driving the observed anti-virulence properties. Overall, this work demonstratesproves the potential of compounds derived from natural sources to inhibit virulence factor production in a clinically important fungal pathogen.

2023-03-06 | PXD038987 | Pride

Chromosome copy number variation in Cryptococcus neoformans influences virulence and occurs in isolates from AIDS patients

Project description:Influence of copy number changes at several chromosomes to melanin production and virulence of Cryptococcus neoformans

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Transcriptomic profiling of the Cryptococcus neoformans transition to titan-like cells

Project description:We compared the expression profile of titan-like cells with cells of regular size in C. neoformans. This was investigated at different time points of the transition: 7 and 24 h

2018-04-20 | GSE111400 | GEO

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