ArticlePLoS genetics2019
Aspergillus fumigatus calcium-responsive transcription factors regulate cell wall architecture promoting stress tolerance, virulence and caspofungin resistance.
Article in PLoS genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
35 citing papers in PubMed, 49 citations in OpenAlex.
- RTA-like proteins regulate azole susceptibility by affecting the expression of the oxidoreductase gene oxrA in Aspergillus fumigatus.BMC microbiology · 2026Article
- The HosA histone deacetylase regulates stress resistance, host cell interactions, and virulence inMicrobiology spectrum · 2026Article
- Characterization of a bZIP Transcription Factor ZipD inMycobiology · 2026Article
- Calcium transport systems as virulence determinants: Mechanistic insights into fungal pathogenicity and antifungal resistance.Virulence · 2025Review
- The HosA histone deacetylase regulates stress resistance, host cell interactions, and virulence inbioRxiv : the preprint server for biology · 2025Article
- Aspergillus fumigatus biology, immunopathogenicity and drug resistance.Nature reviews. Microbiology · 2025Review
- Host-specific adaptation inmBio · 2025Article
- Virulence ofbioRxiv : the preprint server for biology · 2025Article
- Recent developments inMicrobiology and molecular biology reviews : MMBR · 2025Review
- The Influence ofJournal of fungi (Basel, Switzerland) · 2024Article
- The mitochondrial protein Bcs1A regulates antifungal drug tolerance by affecting efflux pump expression in the filamentous pathogenic fungusMicrobiology spectrum · 2024Article
- An oxylipin signal confers protection against antifungal echinocandins in pathogenic aspergilli.Nature communications · 2024Article
- The basic leucine zipper transcription factor MeaB is critical for biofilm formation, cell wall integrity, and virulence inmSphere · 2024Article
- Aspergillus fumigatus mitogen-activated protein kinase MpkA is involved in gliotoxin production and self-protection.Nature communications · 2024Article
- Pathogenicity and virulence ofVirulence · 2023Review
- Transcription factors SltA and CrzA reversely regulate calcium homeostasis under calcium-limited conditions.Applied and environmental microbiology · 2023Article
- A host defense peptide mimetic, brilacidin, potentiates caspofungin antifungal activity against human pathogenic fungi.Nature communications · 2023Article
- Chitin Biosynthesis inJournal of fungi (Basel, Switzerland) · 2023Review
- Genomic and Molecular Identification of Genes Contributing to the Caspofungin Paradoxical Effect inMicrobiology spectrum · 2022Article
- Synergistic Antifungal Effect of a Combination of Iron Deficiency and Calcium Supplementation.Microbiology spectrum · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
19 authors at 7 institutions in 2 countries.
Funding
Abstract
Aspergillus fumigatus causes invasive aspergillosis, the most common life-threatening fungal disease of immuno-compromised humans. The treatment of disseminated infections with antifungal drugs, including echinocandin cell wall biosynthesis inhibitors, is increasingly challenging due to the rise of drug-resistant pathogens. The fungal calcium responsive calcineurin-CrzA pathway influences cell morphology, cell wall composition, virulence, and echinocandin resistance. A screen of 395 A. fumigatus transcription factor mutants identified nine transcription factors important to calcium stress tolerance, including CrzA and ZipD. Here, comparative transcriptomics revealed CrzA and ZipD regulated the expression of shared and unique gene networks, suggesting they participate in both converged and distinct stress response mechanisms. CrzA and ZipD additively promoted calcium stress tolerance. However, ZipD also regulated cell wall organization, osmotic stress tolerance and echinocandin resistance. The absence of ZipD in A. fumigatus caused a significant virulence reduction in immunodeficient and immunocompetent mice. The ΔzipD mutant displayed altered cell wall organization and composition, while being more susceptible to macrophage killing and eliciting an increased pro-inflammatory cytokine response. A higher number of neutrophils, macrophages and activated macrophages were found in ΔzipD infected mice lungs. Collectively, this shows that ZipD-mediated regulation of the fungal cell wall contributes to the evasion of pro-inflammatory responses and tolerance of echinocandin antifungals, and in turn promoting virulence and complicating treatment options.
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Registered trials
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.