ArticleEukaryotic cell2007
Gliotoxin is a virulence factor of Aspergillus fumigatus: gliP deletion attenuates virulence in mice immunosuppressed with hydrocortisone.
Article in Eukaryotic cell, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 130 papers.
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Who cites it
130 citing papers in PubMed, 239 citations in OpenAlex.
- Sputum signatures for invasive pulmonary aspergillosis in patients with underlying respiratory diseases (SPARED): study protocol for a prospective diagnostic trial.BMC infectious diseases · 2018Trial
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- The HosA histone deacetylase regulates stress resistance, host cell interactions, and virulence inMicrobiology spectrum · 2026Article
- Multiplex CRISPR/Cas9 editing of gliotoxin biosynthesis genes in Aspergillus fumigatus reduces pathogenicity in broilers.Brazilian journal of microbiology : [publication of the Brazilian Society for Microbiology] · 2026Article
- Oxidoreductase geneMicrobiology spectrum · 2026Article
- A network-based model of Aspergillus fumigatus elucidates regulators of development and defensive natural products of an opportunistic pathogen.Nucleic acids research · 2026Article
- Molecular mechanisms drivingFrontiers in molecular biosciences · 2026Review
- ULK1 mediated autophagy in airway cells duringFrontiers in microbiology · 2026Article
- Spatial proteomics for the analysis of host-pathogen interactions in mice lungs infected withmicroLife · 2026Article
- Aspergillus fumigatus Gliotoxin Inhibits LC3-Associated Phagocytosis in Macrophages in a Calcium-Dependent Manner.Journal of immunology research · 2026Article
- The HosA histone deacetylase regulates stress resistance, host cell interactions, and virulence inbioRxiv : the preprint server for biology · 2025Article
- Gliotoxin Production and Self-Defense in Filamentous Fungi.Annual review of microbiology · 2025Review
- Progress in Gliotoxin Research.Molecules (Basel, Switzerland) · 2025Review
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- Recent developments inMicrobiology and molecular biology reviews : MMBR · 2025Review
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- The Expanding Mycovirome ofJournal of fungi (Basel, Switzerland) · 2024Review
- Sirtuin E deacetylase is required for full virulence of Aspergillus fumigatus.Communications biology · 2024Article
- The evolution of the gliotoxin biosynthetic gene cluster in Penicillium fungi.G3 (Bethesda, Md.) · 2024Article
70 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 5 institutions in 4 countries.
Funding
Abstract
Gliotoxin is an immunosuppressive mycotoxin long suspected to be a potential virulence factor of Aspergillus fumigatus. Recent studies using mutants lacking gliotoxin production, however, suggested that the mycotoxin is not important for pathogenesis of A. fumigatus in neutropenic mice resulting from treatment with cyclophosphomide and hydrocortisone. In this study, we report on the pathobiological role of gliotoxin in two different mouse strains, 129/Sv and BALB/c, that were immunosuppressed by hydrocortisone alone to avoid neutropenia. These strains of mice were infected using the isogenic set of a wild type strain (B-5233) and its mutant strain (gliPDelta) and the the glip reconstituted strain (gliP(R)). The gliP gene encodes a nonribosomal peptide synthase that catalyzes the first step in gliotoxin biosynthesis. The gliPDelta strain was significantly less virulent than strain B-5233 or gliP(R) in both mouse models. In vitro assays with culture filtrates (CFs) of B-5233, gliPDelta, and gliP(R) strains showed the following: (i) deletion of gliP abrogated gliotoxin production, as determined by high-performance liquid chromatography analysis; (ii) unlike the CFs from strains B-5233 and gliP(R), gliPDelta CFs failed to induce proapoptotic processes in EL4 thymoma cells, as tested by Bak conformational change, mitochondrial-membrane potential disruption, superoxide production, caspase 3 activation, and phosphatidylserine translocation. Furthermore, superoxide production in human neutrophils was strongly inhibited by CFs from strain B-5233 and the gliP(R) strain, but not the gliPDelta strain. Our study confirms that gliotoxin is an important virulence determinant of A. fumigatus and that the type of immunosuppression regimen used is important to reveal the pathogenic potential of gliotoxin.
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