ArticleNature communications2024
Functional analysis of the Aspergillus fumigatus kinome identifies a druggable DYRK kinase that regulates septal plugging.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed.
- Barcoded mutant library enables high-throughput functional genomics in a filamentous fungus.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
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- STRIPAK-associated greenbeard proteins DOC1 and DOC2 regulate MAK2 signaling and sexual development in Sordaria macrospora.PLoS biology · 2026Article
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- Construction of a randomly barcoded insertional mutant library in the filamentous fungusbioRxiv : the preprint server for biology · 2025Article
- The sulfur-related metabolic status ofVirulence · 2025Article
- Loss of theMicrobiology spectrum · 2025Article
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- Colistin enhances caspofungin antifungal efficacy against Aspergillus fumigatus by modulating calcium homeostasis and stress responses.Nature communications · 2025Article
- Unravelling fungal genome editing revolution: pathological and biotechnological application aspects.Archives of microbiology · 2025Review
- A novel pan-fungal screening platform for antifungal drug discovery: proof of principle study.Antimicrobial agents and chemotherapy · 2025Article
- Recent developments inMicrobiology and molecular biology reviews : MMBR · 2025Review
- Harnessing the Tet-Off system for effective gene silencing inFrontiers in plant science · 2025Article
- Development and optimization of large-scale approaches to identify iron-related genes inFrontiers in microbiology · 2025Article
- Reply to: Lactobacillus species do not produce 1-acetyl-β-carboline.Nature communications · 2024Article
Corrections and comments
- Erratum issued
- Update of
Authors and funding
21 authors.
Funding
Abstract
More than 10 million people suffer from lung diseases caused by the pathogenic fungus Aspergillus fumigatus. Azole antifungals represent first-line therapeutics for most of these infections but resistance is rising, therefore the identification of antifungal targets whose inhibition synergises with the azoles could improve therapeutic outcomes. Here, we generate a library of 111 genetically barcoded null mutants of Aspergillus fumigatus in genes encoding protein kinases, and show that loss of function of kinase YakA results in hypersensitivity to the azoles and reduced pathogenicity. YakA is an orthologue of Candida albicans Yak1, a TOR signalling pathway kinase involved in modulation of stress responsive transcriptional regulators. We show that YakA has been repurposed in A. fumigatus to regulate blocking of the septal pore upon exposure to stress. Loss of YakA function reduces the ability of A. fumigatus to penetrate solid media and to grow in mouse lung tissue. We also show that 1-ethoxycarbonyl-beta-carboline (1-ECBC), a compound previously shown to inhibit C. albicans Yak1, prevents stress-mediated septal spore blocking and synergises with the azoles to inhibit A. fumigatus growth.
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