A5065090381- Antifungal resistance and susceptibility
- Fungal and yeast genetics research
- Mycotoxins in Agriculture and Food
- Fungal Infections and Studies
- Microbial Natural Products and Biosynthesis
- Fungal Biology and Applications
- Peptidase Inhibition and Analysis
- Chemical Synthesis and Analysis
- Plant Pathogens and Fungal Diseases
- Plant Reproductive Biology
- Plant Molecular Biology Research
- Plant-Microbe Interactions and Immunity
- Cellular transport and secretion
- Plant tissue culture and regeneration
- Redox biology and oxidative stress
- Polysaccharides and Plant Cell Walls
- Antimicrobial Peptides and Activities
- Insect symbiosis and bacterial influences
- Gut microbiota and health
- Genomics, phytochemicals, and oxidative stress
- Plant Gene Expression Analysis
- Insect and Pesticide Research
- Plant biochemistry and biosynthesis
- Synthesis and Biological Evaluation
- Bacterial biofilms and quorum sensing
Leibniz-Institut für Naturstoff-Forschung und Infektionsbiologie e. V. - Hans-Knöll-Institut (HKI)
2016-2025
Friedrich Schiller University Jena
2008-2024
Leibniz Association
2008-2023
University of Göttingen
2001-2004
ABSTRACT To increase the frequency of homologous recombination, we inactivated KU80 homologue in Aspergillus fumigatus (named akuB ). Homologous integration reached about 80% for both calcineurin A ( calA ) and polyketide synthase pksP (alb1 genes mutant to 3 5%, respectively, when using a wild-type A. strain. Deletion had no influence on pathogenicity low-dose murine infection model.
Iron is essential for a wide range of cellular processes. Here we show that the bZIP-type regulator HapX indispensable transcriptional remodeling required adaption to iron starvation in opportunistic fungal pathogen Aspergillus fumigatus. represses iron-dependent and mitochondrial-localized activities including respiration, TCA cycle, amino acid metabolism, iron-sulfur-cluster heme biosynthesis. In agreement with impact on mitochondrial HapX-deficiency decreases resistance tetracycline...
The opportunistic human pathogenic fungus Aspergillus fumigatus produces at least two types of melanin, namely pyomelanin and dihydroxynaphthalene (DHN) melanin. Pyomelanin is produced during tyrosine catabolism via accumulation homogentisic acid. Although protects the against reactive oxygen species acts as a defense compound in response to cell wall stress, mutants deficient for biosynthesis do not differ virulence when tested murine infection model invasive pulmonary aspergillosis. DHN...
Aspergillus fumigatus, the most common airborne fungal pathogen of humans, employs two high-affinity iron uptake systems: mediated by extracellular siderophore triacetylfusarinine C and reductive assimilation. Furthermore, A. fumigatus utilizes intracellular siderophores, ferricrocin hydroxyferricrocin, to store iron. Siderophore biosynthesis, which is essential for virulence, repressed Here we show that this control GATA factor SreA. During iron-replete conditions, SreA deficiency partially...
Aspergillus fumigatus is the most important airborne fungal pathogen of immunosuppressed humans. A. able to produce dihydroxynaphthalene melanin, which predominantly present in conidia. Its biosynthesis an virulence determinant. Here, we show that alternative i.e., pyomelanin, by a different pathway, starting from L-tyrosine. Proteome analysis indicated l-tyrosine degradation enzymes are synthesized when fungus grown with L-tyrosine medium. To investigate pathway detail, deleted genes...
Aspergillus fumigatus is the most important air-borne fungal pathogen of humans. The interaction with host's immune system represents a key process to understand pathogenicity. For elimination invading microorganisms, they need be efficiently phagocytosed and located in acidified phagolysosomes. However, as shown previously, A. able manipulate formation functional Here, we demonstrate that contrast pigmentless pksP mutant conidia fumigatus, gray-green wild-type inhibit acidification...
Gliotoxin (1), the infamous representative of group epipolythiodioxopiperazines (ETPs), is a virulence factor human pathogenic fungus Aspergillus fumigatus. The unique redox-sensitive transannular disulfide bridge critical for deleterious effects caused by redox cycling and protein conjugation in host. Through combination genetic, biochemical, chemical analyses, we found that 1 results from GliT-mediated oxidation corresponding dithiol. In vitro studies using purified GliT demonstrate...
Summary The saprophytic fungus Aspergillus fumigatus is the most important air‐borne fungal pathogen. cell wall of A. has been studied intensively as a potential target for development effective antifungal agents. A major role in maintaining integrity played by mitogen‐activated protein kinase (MAPK) MpkA. To gain comprehensive insight into this central signal transduction pathway, we performed transcriptome analysis Δ mpkA mutant under standard and stress conditions. Besides genes involved...
Gliotoxin is a virulence factor of the human pathogen Aspergillus fumigatus, leading cause invasive aspergillosis. Its toxicity mediated by unusual transannular disulfide bridge epidithiodiketopiperazine (ETP) scaffold. Here we disclose critical role specialized glutathione S-transferase (GST), GliG, in enzymatic sulfurization. Furthermore, show that bishydroxylation diketopiperazine oxygenase GliC prerequisite for adduct formation. This first report involvement GST C–S bond formation...
Summary Filamentous fungi represent classical examples for environmentally acquired human pathogens whose major virulence mechanisms are likely to have emerged long before the appearance of innate immune systems. In natural habitats, amoeba predation could impose a selection pressure towards acquisition attributes. To test this hypothesis, we exploited Dictyostelium discoideum study its interaction with A spergillus fumigatus , two abundant soil inhabitants which found co‐occurrence in...
The decision whether endosomes enter the degradative or recycling pathway in mammalian cells is of fundamental importance for pathogen killing, and its malfunctioning has pathological consequences. We discovered that human p11 a critical factor this decision. HscA protein present on conidial surface human-pathogenic fungus Aspergillus fumigatus anchors conidia-containing phagosomes (PSs), excludes PS maturation mediator Rab7, triggers binding exocytosis mediators Rab11 Sec15. This...
Gliotoxin is a secondary metabolite produced by several fungi including the opportunistic human pathogen Aspergillus fumigatus. As gliotoxin exerts immunosuppressive effects in vitro and vivo, role as virulence determinant invasive aspergillosis has been discussed for long time but evidence not provided until now. Here, use of different selection marker genes A. fumigatus knock-out strains were generated that are deficient non-ribosomal peptide synthetase GliP, putative key enzyme...
Gliotoxin (1), a virulence factor of the human pathogenic fungus Aspergillus fumigatus, is prototype epipoly(thiodioxopiperazine) (ETP) toxins. Here we report discovery and functional analysis two methyl transferases (MTs) that play crucial roles for ETP toxicity. Genome comparisons, knockouts, in vitro enzyme studies identified new S-adenosyl-l-methionine-dependent S-MT (TmtA) is, surprisingly, encoded outside gli gene cluster. We found TmtA irreversibly inactivates by S-alkylation this...
The mammalian immune system relies on recognition of pathogen surface antigens for targeting and clearance. In the absence evasion strategies, clearance is rapid. case Aspergillus fumigatus , successful fungus must avoid phagocytosis in lung to establish invasive infection. healthy individuals, fungal spores are cleared by cells; however, immunocompromised patients, mechanisms impaired. Here, using proteome analyses, we identified CcpA as an important spore protein involved pathogenesis. A....
Lipid rafts form signaling platforms on biological membranes with incompletely characterized role in immune response to infection. Here we report that lipid-raft microdomains are essential components of phagolysosomal macrophages and depend flotillins. Genetic deletion flotillins demonstrates the assembly both major defense complexes vATPase NADPH oxidase requires membrane microdomains. Furthermore, describe a virulence mechanism leading dysregulation by melanized wild-type conidia important...
Aspergillus fumigatus, an opportunistic human pathogen, frequently infects the lungs of people with cystic fibrosis and is one most common causes infectious-disease death in immunocompromised patients. Here, we construct 252 strain-specific, genome-scale metabolic models this important fungal pathogen to study better understand component its pathogenic versatility. The show that 23.1% A. fumigatus reactions are not conserved across strains mainly associated amino acid, nucleotide, nitrogen...
Aspergillus fumigatus is an opportunistic human pathogenic fungus causing severe infections in immunocompromised patients. Cyclic AMP (cAMP) signal transduction plays important role virulence. A central component of this signaling cascade protein kinase (PKA), which regulates cellular processes by phosphorylation specific target proteins. Here we describe the generation and analysis A. mutants expressing gene encoding catalytic subunit PKA, pkaC1, under control inducible promoter. Strains...