Analysis of the Aspergillus fumigatus proteome reveals metabolic changes and the activation of the pseurotin A biosynthesis gene cluster in response to hypoxia.

The mold Aspergillus fumigatus is the most important airborne fungal pathogen. Adaptation to hypoxia represents an important virulence attribute for A. fumigatus.

Comparative and functional genomics provide insights into the pathogenicity of dermatophytic fungi.

Background: Millions of humans and animals suffer from superficial infections caused by a group of highly specialized filamentous fungi, the dermatophytes, which exclusively infect keratinized host structures. To provide broad insights into the molecular basis of the pathogenicity-associated traits, we report the first genome sequences of two closely phylogenetically related dermatophytes, Arthroderma benhamiae and Trichophyton verrucosum, both of which induce highly inflammatory infections in humans.

Results: 97% of the 22.

FungiFun: a web-based application for functional categorization of fungal genes and proteins.

FungiFun assigns functional annotations to fungal genes or proteins and performs gene set enrichment analysis. Based on three different classification methods (FunCat, GO and KEGG), FungiFun categorizes genes and proteins for several fungal species on different levels of annotation detail. It is web-based and accessible to users without any programming skills.

Activation of a silent fungal polyketide biosynthesis pathway through regulatory cross talk with a cryptic nonribosomal peptide synthetase gene cluster.

Filamentous fungi produce numerous natural products that constitute a consistent source of potential drug leads, yet it seems that the majority of natural products are overlooked since most biosynthesis gene clusters are silent under standard cultivation conditions. Screening secondary metabolite genes of the model fungus Aspergillus nidulans, we noted a silent gene cluster on chromosome II comprising two nonribosomal peptide synthetase (NRPS) genes, inpA and inpB, flanked by a regulatory gene that we named scpR for secondary metabolism cross-pathway regulator. The induced expression of the scpR gene using the promoter of the alcohol dehydrogenase AlcA led to the transcriptional activation of both the endogenous scpR gene and the NRPS genes.

HapX-mediated adaption to iron starvation is crucial for virulence of Aspergillus fumigatus.

Iron is essential for a wide range of cellular processes. Here we show that the bZIP-type regulator HapX is indispensable for the transcriptional remodeling required for adaption to iron starvation in the opportunistic fungal pathogen Aspergillus fumigatus. HapX represses iron-dependent and mitochondrial-localized activities including respiration, TCA cycle, amino acid metabolism, iron-sulfur-cluster and heme biosynthesis.

Functional genomic profiling of Aspergillus fumigatus biofilm reveals enhanced production of the mycotoxin gliotoxin.

The opportunistic pathogenic mold Aspergillus fumigatus is an increasing cause of morbidity and mortality in immunocompromised and in part immunocompetent patients. A. fumigatus can grow in multicellular communities by the formation of a hyphal network encased in an extracellular matrix.

Interaction of phagocytes with filamentous fungi.

Phagocytosis of conidia by macrophages and destruction of hyphae by neutrophils are key processes in the defense against infections caused by filamentous fungi. Impairment in phagocytic function leads to increased susceptibility for an infection with Aspergillus species. The fact that a Th1-based immune response to an infection with Aspergillus species results in an improved prognosis for survival underlines the importance of the phagocytic response.

Transannular disulfide formation in gliotoxin biosynthesis and its role in self-resistance of the human pathogen Aspergillus fumigatus.

Gliotoxin (1), the infamous representative of the group of epipolythiodioxopiperazines (ETPs), is a virulence factor of the human pathogenic fungus Aspergillus fumigatus. The unique redox-sensitive transannular disulfide bridge is critical for deleterious effects caused by redox cycling and protein conjugation in the host. Through a combination of genetic, biochemical, and chemical analyses, we found that 1 results from GliT-mediated oxidation of the corresponding dithiol.

Proteome profiling and functional classification of intracellular proteins from conidia of the human-pathogenic mold Aspergillus fumigatus.

Aspergillus fumigatus is a ubiquitously distributed filamentous fungus that has emerged as one of the most serious life-threatening pathogens in immunocompromised patients. The mechanisms for its pathogenicity are poorly understood. Here, we analyzed the proteome of dormant A.

Secreted Aspergillus fumigatus protease Alp1 degrades human complement proteins C3, C4, and C5.

The opportunistic human pathogenic fungus Aspergillus fumigatus is a major cause of fungal infections in immunocompromised patients. Innate immunity plays an important role in the defense against infections. The complement system represents an essential part of the innate immune system.

Production of extracellular traps against Aspergillus fumigatus in vitro and in infected lung tissue is dependent on invading neutrophils and influenced by hydrophobin RodA.

Aspergillus fumigatus is the most important airborne fungal pathogen causing life-threatening infections in immunocompromised patients. Macrophages and neutrophils are known to kill conidia, whereas hyphae are killed mainly by neutrophils. Since hyphae are too large to be engulfed, neutrophils possess an array of extracellular killing mechanisms including the formation of neutrophil extracellular traps (NETs) consisting of nuclear DNA decorated with fungicidal proteins.

Fungal secondary metabolites - strategies to activate silent gene clusters.

Filamentous fungi produce a multitude of low molecular weight bioactive compounds. The increasing number of fungal genome sequences impressively demonstrated that their biosynthetic potential is far from being exploited. In fungi, the genes required for the biosynthesis of a secondary metabolite are clustered.

Heptahelical receptors GprC and GprD of Aspergillus fumigatus Are essential regulators of colony growth, hyphal morphogenesis, and virulence.

The filamentous fungus Aspergillus fumigatus normally grows on compost or hay but is also able to colonize environments such as the human lung. In order to survive, this organism needs to react to a multitude of external stimuli. Although extensive work has been carried out to investigate intracellular signal transduction in A.

Members of protein O-mannosyltransferase family in Aspergillus fumigatus differentially affect growth, morphogenesis and viability.

O-mannosylation is an essential protein modification in eukaryotes. It is initiated at the endoplasmic reticulum by O-mannosyltransferases (PMT) that are evolutionary conserved from yeast to humans. The PMT family is phylogenetically classified into PMT1, PMT2 and PMT4 subfamilies, which differ in protein substrate specificity and number of genes per subfamily.

Missing values in gel-based proteomics.

Gel-based proteomics is a widely applied technique to measure abundances of proteins in various biological systems. Comparison of two or more biological groups involves matching of 2-D gels. Depending on the software, this can result in spots showing missing values on several gels.

Integrative analysis of the heat shock response in Aspergillus fumigatus.

Background: Aspergillus fumigatus is a thermotolerant human-pathogenic mold and the most common cause of invasive aspergillosis (IA) in immunocompromised patients. Its predominance is based on several factors most of which are still unknown. The thermotolerance of A.

The CCAAT-binding complex coordinates the oxidative stress response in eukaryotes.

The heterotrimeric CCAAT-binding complex is evolutionary conserved in eukaryotic organisms. The corresponding Aspergillus nidulans CCAAT-binding factor (AnCF) consists of the subunits HapB, HapC and HapE. All of the three subunits are necessary for DNA binding.

Aspects on evolution of fungal beta-lactam biosynthesis gene clusters and recruitment of trans-acting factors.

Penicillins and cephalosporins are beta-lactam antibiotics. The formation of hydrophobic penicillins has been reported in fungi only, notably Penicillium chrysogenum and Aspergillus (Emericella) nidulans, whereas the hydrophilic cephalosporins are produced by both fungi, e.g.

The MpkA MAP kinase module regulates cell wall integrity signaling and pyomelanin formation in Aspergillus fumigatus.

Aspergillus fumigatus is the most important air-borne fungal pathogen, causing severe infections in immunocompromised patients. Mitogen-activated protein kinase (MAPK) signaling pathways are involved in the regulation of various cellular responses to environmental changes in eukaryotes. Genome Blast analysis revealed that the central core of the cell wall integrity signaling pathway in A.

Surface hydrophobin prevents immune recognition of airborne fungal spores.

The air we breathe is filled with thousands of fungal spores (conidia) per cubic metre, which in certain composting environments can easily exceed 10(9) per cubic metre. They originate from more than a hundred fungal species belonging mainly to the genera Cladosporium, Penicillium, Alternaria and Aspergillus. Although these conidia contain many antigens and allergens, it is not known why airborne fungal microflora do not activate the host innate immune cells continuously and do not induce detrimental inflammatory responses following their inhalation.

Intimate bacterial-fungal interaction triggers biosynthesis of archetypal polyketides in Aspergillus nidulans.

Fungi produce numerous low molecular weight molecules endowed with a multitude of biological activities. However, mining the full-genome sequences of fungi indicates that their potential to produce secondary metabolites is greatly underestimated. Because most of the biosynthesis gene clusters are silent under laboratory conditions, one of the major challenges is to understand the physiological conditions under which these genes are activated.

Comparative genomics of MAP kinase and calcium-calcineurin signalling components in plant and human pathogenic fungi.

Mitogen-activated protein kinase (MAPK) cascades and the calcium-calcineurin pathway control fundamental aspects of fungal growth, development and reproduction. Core elements of these signalling pathways are required for virulence in a wide array of fungal pathogens of plants and mammals. In this review, we have used the available genome databases to explore the structural conservation of three MAPK cascades and the calcium-calcineurin pathway in ten different fungal species, including model organisms, plant pathogens and human pathogens.

Two-dimensional proteome reference maps for the human pathogenic filamentous fungus Aspergillus fumigatus.

The filamentous fungus Aspergillus fumigatus has become the most important airborne fungal pathogen causing life-threatening infections in immunosuppressed patients. We established a 2-D reference map for A. fumigatus.

Contribution of peroxisomes to penicillin biosynthesis in Aspergillus nidulans.

Peroxisomal localization of the third enzyme of the penicillin biosynthesis pathway of Aspergillus nidulans, acyl-coenzyme A:IPN acyltransferase (IAT), is mediated by its atypical peroxisomal targeting signal 1 (PTS1). However, mislocalization of IAT by deletion of either its PTS1 or of genes encoding proteins involved in peroxisome formation or transport does not completely abolish penicillin biosynthesis. This is in contrast to the effects of IAT mislocalization in Penicillium chrysogenum.