ArticlePloS one2015
Network Modeling Reveals Cross Talk of MAP Kinases during Adaptation to Caspofungin Stress in Aspergillus fumigatus.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 65 citations in OpenAlex.
- A network-based model of Aspergillus fumigatus elucidates regulators of development and defensive natural products of an opportunistic pathogen.Nucleic acids research · 2026Article
- The Influence ofJournal of fungi (Basel, Switzerland) · 2024Article
- An oxylipin signal confers protection against antifungal echinocandins in pathogenic aspergilli.Nature communications · 2024Article
- Characterization and engineering of the xylose-inducibleMetabolic engineering communications · 2022Article
- Stimulating fungal cell wall integrity by exogenous β-glucanase to improve the production of fungal natural products.Applied microbiology and biotechnology · 2022Article
- Genomic and Molecular Identification of Genes Contributing to the Caspofungin Paradoxical Effect inMicrobiology spectrum · 2022Article
- The Anti-Fungal Activity of Nitropropenyl Benzodioxole (NPBD), a Redox-Thiol Oxidant and Tyrosine Phosphatase Inhibitor.Antibiotics (Basel, Switzerland) · 2022Article
- MAPK CcSakA of the HOG Pathway Is Involved in Stipe Elongation during Fruiting Body Development inJournal of fungi (Basel, Switzerland) · 2022Article
- Fus3, as a Critical Kinase in MAPK Cascade, Regulates Aflatoxin Biosynthesis by Controlling the Substrate Supply in Aspergillus flavus, Rather than the Cluster Genes Modulation.Microbiology spectrum · 2022Article
- Crosstalk between the calcineurin and cell wall integrity pathways prevents chitin overexpression in Candida albicans.Journal of cell science · 2021Article
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- Loss of Septation Initiation Network (SIN) kinases blocks tissue invasion and unlocks echinocandin cidal activity against Aspergillus fumigatus.PLoS pathogens · 2021Article
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- Aspergillus fumigatus Hsp90 interacts with the main components of the cell wall integrity pathway and cooperates in heat shock and cell wall stress adaptation.Cellular microbiology · 2021Article
- The Heat Shock Transcription Factor HsfA Is Essential for Thermotolerance and Regulates Cell Wall Integrity inFrontiers in microbiology · 2021Article
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- Fungal oxylipins direct programmed developmental switches in filamentous fungi.Nature communications · 2020Article
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- Aspergillus fumigatus Transcription Factors Involved in the Caspofungin Paradoxical Effect.mBio · 2020Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mitogen activated protein kinases (MAPKs) are highly conserved in eukaryotic organisms. In pathogenic fungi, their activities were assigned to different physiological functions including drug adaptation and resistance. Aspergillus fumigatus is a human pathogenic fungus, which causes life-threatening invasive infections. Therapeutic options against invasive mycoses are still limited. One of the clinically used drugs is caspofungin, which specifically targets the fungal cell wall biosynthesis. A systems biology approach, based on comprehensive transcriptome data sets and mathematical modeling, was employed to infer a regulatory network and identify key interactions during adaptation to caspofungin stress in A. fumigatus. Mathematical modeling and experimental validations confirmed an intimate cross talk occurring between the cell wall-integrity and the high osmolarity-glycerol signaling pathways. Specifically, increased concentrations of caspofungin promoted activation of these signalings. Moreover, caspofungin affected the intracellular transport, which caused an additional osmotic stress that is independent of glucan inhibition. High concentrations of caspofungin reduced this osmotic stress, and thus decreased its toxic activity. Our results demonstrated that MAPK signaling pathways play a key role during caspofungin adaptation and are contributing to the paradoxical effect exerted by this drug.
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