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ABSTRACT: Interactions of an emerging fungal pathogen Scedosporium aurantiacum with human lung epithelial cells

PROVIDER: PRJNA495879 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR8049180_1.fastq.gz	Fastqsanger.gz
	SRR8049180_2.fastq.gz	Fastqsanger.gz
	SRR8049181_1.fastq.gz	Fastqsanger.gz
	SRR8049181_2.fastq.gz	Fastqsanger.gz
	SRR8049176_1.fastq.gz	Fastqsanger.gz

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Project description:Respiratory fungal infections pose a significant threat to human health, but animal models do not fully recapitulate human disease, necessitating advanced models to study human-fungal pathogen interactions. In this study, we utilized primary human airway epithelial cells (hAECs) to recapitulate the lung environment in vitro and investigate cellular responses to two diverse, clinically significant fungal pathogens, Aspergillus fumigatus and Coccidioides posadasii. To understand the mechanisms of early pathogenesis for both fungi, we performed single-cell RNA sequencing of infected hAECs. Analysis revealed that both fungi induced cellular stress and cytokine production. However, the cell subtypes affected and specific pathways differed between fungi, with A. fumigatus and C. posadasii triggering protein-folding-related stress in ciliated cells and hypoxia responses in secretory cells, respectively. This study represents one of the first reports of single-cell transcriptional analysis of hAECs infected with either A. fumigatus or C. posadasii, providing a vital dataset to dissect the mechanism of disease and potentially identify targetable pathways.

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Project description:In lung diseases caused by the major mould pathogen Aspergillus fumigatus the pulmonary epithelium is destroyed by invasive growth of fungal hyphae, a process thought to require fungal proteases. Here we show that the A. fumigatus pH-responsive transcription factor PacC governs expression of secreted proteases during invasive lung infections and is required for epithelial invasion and pathogenicity. In addition, A. fumigatus ΔpacC mutants aberrantly remodel the fungal cell wall during infection. This study defines distinct PacC-mediated mechanisms of host damage during pulmonary aspergillosis. ch1: treatment protocol

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