ArticlePLoS pathogens2009
A role for the unfolded protein response (UPR) in virulence and antifungal susceptibility in Aspergillus fumigatus.
Article in PLoS pathogens, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 114 papers.
What it found
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Who cites it
114 citing papers in PubMed, 186 citations in OpenAlex.
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- Hypovirus-Induced Phosphorylation of CpIre1 Modulates Unfolded Protein Response and Virulence in Cryphonectria parasitica.Molecular plant pathology · 2026Article
- Integrative computational-experimental discovery and translation of antifungal peptides for multidrug-resistant fungi.Frontiers in microbiology · 2026Review
- A stress responsive protein contributes to pyomelanin biosynthesis and cell wall stress adaptation inFrontiers in microbiology · 2026Article
- ER stress selects forFrontiers in microbiology · 2026Article
- Pathogenic mucorales: Deciphering their cell wall polysaccharidome and immunostimulatory potential.Virulence · 2025Article
- Chromosome-level comparative genomics and host-specific fungal transcriptomics uncover adaptive virulence strategies in the sugarcane smut pathogen.BMC genomics · 2025Article
- Dual Role of MtHAC-1 in Regulating Cellulase and Xylanase Production in Myceliophthora thermophila.Microbial biotechnology · 2025Article
- Recent developments inMicrobiology and molecular biology reviews : MMBR · 2025Review
- Modification of essential factors mediating post-translational processing for high-quality protein expression inEngineering microbiology · 2025Article
- Role of cell membrane homeostasis in the pathogenicity of pathogenic filamentous fungi.Virulence · 2024Review
- Protein secretion and associated stress in industrially employed filamentous fungi.Applied microbiology and biotechnology · 2024Review
- TheJournal of fungi (Basel, Switzerland) · 2024Article
- Comparative Analysis of the Aspergillus fumigatus Cell Wall Modification and Ensuing Human Dendritic Cell Responses by β-(1,3)-Glucan Synthase Inhibitors-Caspofungin and Enfumafungin.Mycopathologia · 2024Article
- The mammalian Ire1 inhibitor, 4μ8C, exhibits broad anti-bioRxiv : the preprint server for biology · 2024Article
- Multi-omics analysis revealed that the protein kinase MoKin1 affected the cellular response to endoplasmic reticulum stress in the rice blast fungus, Magnaporthe oryzae.BMC genomics · 2024Article
- Fungi of the order Mucorales express a "sealing-only" tRNA ligase.RNA (New York, N.Y.) · 2024Article
- The mammalian Ire1 inhibitor, 4µ8C, exhibits broad anti-Frontiers in cellular and infection microbiology · 2024Article
- Fungi of the order Mucorales express a "sealing-only" tRNA ligase.bioRxiv : the preprint server for biology · 2023Article
54 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
Filamentous fungi rely heavily on the secretory pathway, both for the delivery of cell wall components to the hyphal tip and the production and secretion of extracellular hydrolytic enzymes needed to support growth on polymeric substrates. Increased demand on the secretory system exerts stress on the endoplasmic reticulum (ER), which is countered by the activation of a coordinated stress response pathway termed the unfolded protein response (UPR). To determine the contribution of the UPR to the growth and virulence of the filamentous fungal pathogen Aspergillus fumigatus, we disrupted the hacA gene, encoding the major transcriptional regulator of the UPR. The DeltahacA mutant was unable to activate the UPR in response to ER stress and was hypersensitive to agents that disrupt ER homeostasis or the cell wall. Failure to induce the UPR did not affect radial growth on rich medium at 37 degrees C, but cell wall integrity was disrupted at 45 degrees C, resulting in a dramatic loss in viability. The DeltahacA mutant displayed a reduced capacity for protease secretion and was growth-impaired when challenged to assimilate nutrients from complex substrates. In addition, the DeltahacA mutant exhibited increased susceptibility to current antifungal agents that disrupt the membrane or cell wall and had attenuated virulence in multiple mouse models of invasive aspergillosis. These results demonstrate the importance of ER homeostasis to the growth and virulence of A. fumigatus and suggest that targeting the UPR, either alone or in combination with other antifungal drugs, would be an effective antifungal strategy.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.