Frank Ebel

Ludwig-Maximilians-University of Munich | LMU · Institute for Infectious Diseases and Zoonoses

Stachybotrys chartarum is a toxigenic fungus that is frequently isolated from damp building materials or improperly stored forage. Macrocyclic trichothecenes and in particular satratoxins are the most potent mycotoxins known to be produced by this fungus. Exposure of humans or animals to these secondary metabolites can be associated with severe hea...

All Aspergillus species form phialidic conidia (PC) when the mycelium is in contact with the air. These small, asexual spores are ideally suited for an airborne dissemination in the environment. Aspergillus terreus and a few closely related species from section Terrei can additionally generate accessory conidia (AC) that directly emerge from the hy...

Stachybotrys chartarum is frequently isolated from damp building materials or improperly stored animal forage. Human and animal exposure to the secondary metabolites of this mold is linked to severe health effects. The mutually exclusive production of either satratoxins or atranones defines the chemotypes A and S. Based upon the genes (satratoxin c...

Aspergillus fumigatus is a major fungal pathogen causing life threatening infections in immunocompromised humans and certain animals. The HOG pathway is for two reasons interesting in this context: firstly, it is a stress signaling pathway that contributes to the ability of this pathogen to adapt to various stress conditions and secondly, it is the...

Occupational mold exposure can lead to Aspergillus-associated allergic diseases including asthma and hypersensitivity pneumonitis. Elevated IL-17 levels or disbalanced T-helper (Th) cell expansion were previously linked to Aspergillus-associated allergic diseases, whereas alterations to the Th cell repertoire in healthy occupationally exposed subje...

The ascomycete fungus Fusarium oxysporum f.sp. cucumerinum causes vascular wilt diseases in cucumber. However, few genes related to morphogenesis and pathogenicity of this fungal pathogen have been functionally characterized. BLASTp searches of the Aspergillus fumigatus UgmA and galatofuranosyltransferases (Galf-transferases) sequences in the F. ox...

Deeper understanding of mold-induced cytokine signatures could promote advances in the diagnosis and treatment of invasive mycoses and mold-associated hypersensitivity syndromes. Currently, most T-cellular immunoassays in medical mycology require the isolation of mononuclear cells and have limited robustness and practicability, hampering their broa...

Aspergillus fumigatus is an important fungal pathogen that represents a major threat for severely immunocompromised patients. Cases of invasive aspergillosis are associated with a high mortality rate, which reflects the limited treatment options that are currently available. The development of novel therapeutic approaches is therefore an urgent tas...

Straw is the main by-product of grain production, used as bedding material and animal feed. If produced or stored under adverse hygienic conditions, straw is prone to the growth of filamentous fungi. Some of them, e.g., Aspergillus, Fusarium, and Stachybotrys spp. are well-known mycotoxin producers. Since studies on mycotoxins in straw are scarce,...

Antibodies represent an important element in the adaptive immune response and a major tool to eliminate microbial pathogens. For many bacterial and viral infections, efficient vaccines exist, but not for fungal pathogens. For a long time, antibodies have been assumed to be of minor importance for a successful clearance of fungal infections; however...

Aspergillus fumigatus and A. flavus are the fungal pathogens responsible for most cases of invasive aspergillosis (IA). Early detection of the circulating antigen galactomannan (GM) in serum allows the prompt application of effective antifungal therapy, thus improving the survival rate of IA patients. However, the use of monoclonal antibodies (mAbs...

In filamentous fungi, group III hybrid histidine kinases (HHKs) are major and nonredundant sensing proteins of the high osmolarity glycerol pathway. In this study, we have compared the biological functions of the two homologous group III HHKs TcsC of Aspergillus fumigatus and NikA of A. nidulans. As expected from previous studies, the corresponding...

Aim: Immunofluorescence microscopy is a powerful technique to detect surface antigens and study their distribution. Analysis of fungi is often hampered by their weak adherence to glass. We therefore established a novel immunofluorescence staining method to overcome this problem. Materials & methods: Fungal material from colonies is bound to adhe...

Interactions between fungal pathogens such as Aspergillus fumigatus with host alveolar epithelium and innate immune cells are crucial in the defense against opportunistic fungal infections. In this study a simplified Transwell® system with a confluent layer of A549 cells acted as a model for the alveolar surface. A. fumigatus and dendritic cells we...

Invasive fungal infections can cause significant morbidity and mortality in humans and different animal species, worldwide. Antifungal therapy remains a central component of protecting human and vertebrate animals against fungal infections. Depending on the strategy chosen, topical and/or systemic drugs can be used based on the clinical picture of...

The importance of fungal infections in both human and animals has increased over the last decades. This article represents an overview of the different categories of fungal infections that can be encountered in animals originating from environmental sources without transmission to humans. In addition, the endemic infections with indirect transmissi...

Fungal hyphae constitute a special challenge for the immune system, since they are too large to be phagocytosed. This review summarizes our current knowledge on those immune cells that are able to attack and eliminate hyphae and we discuss the different means that are employed by these cells in order to kill hyphae.

The type III hybrid histidine kinase (HHK) TcsC enables the pathogenic mold Aspergillus fumigatus to thrive under hyperosmotic conditions. It is, moreover, of particular interest, since it is the target of certain antifungal agents, such as fludioxonil. This study was aimed at a functional characterization of the domains that constitute the sensing...

Woronin bodies are specialized, fungal-specific organelles that enable an immediate closure of septal pores after injury to protect hyphae from excessive cytoplasmic bleeding. In most Ascomycetes, Woronin bodies are tethered at the septal pore by so-called Lah proteins. Using the pathogenic mold Aspergillus fumigatus as a model organism, we show th...

Invasive pulmonary aspergillosis is a life-threatening mycosis that only affects patients with immunosuppression, chemotherapy-induced neutropenia, transplantation, or congenital immunodeficiency. We studied the clinical, genetic, histological, and immunological features of 2 unrelated patients without known immunodeficiency who developed extrapulm...

Treatment of invasive fungal infections often fails due to the limited number of therapeutic options. In this study, we have analyzed the impact of agents activating the High Osmolarity Glycerol (HOG) pathway on molds that cause infections in humans and livestock. We found that agents like fludioxonil and iprodione, have a clear anti-fungal activit...

Filamentous fungi of the genus Aspergillus play significant roles as pathogens causing superficial and invasive infections as well as allergic reactions in humans. Particularly invasive mycoses caused by Aspergillus species are characterised by high mortality rates due to difficult diagnosis and insufficient antifungal therapy. The application of i...

Detection of carbohydrate antigens is an important means for diagnosis of invasive fungal infections. For diagnosis of systemic Aspergillus infections, galactomannan is commonly used, the core antigenic structure of which consists of chains of several galactofuranose moieties. In this study, we provide evidence that Fusarium produces at least two d...

Woronin bodies are fungal-specific organelles that seal damaged hyphal compartments and thereby contribute to the stress resistance and virulence of filamentous fungi. In this study, we have characterized the Aspergillus fumigatus Woronin body protein WscA. WscA is homologous to Neurospora crassa WSC, a protein that was shown to be important for bi...

The mold Aspergillus fumigatus causes life-threatening infections in immunocompromised patients. Over the past decade, new findings in research have improved our understanding of A. fumigatus-host interactions, including the recent identification of myeloid-expressed hypoxia-inducible factor 1α (HIF-1α) as a relevant immune-modulating transcription...

Echinocandins inhibit β-1,3-glucan synthesis and are one of the few antimycotic drug classes 3 effective against Aspergillus spp. In this study we characterized the β-1,3-glucan synthase 4 Fks1 of Aspergillus fumigatus, the putative target of echinocandins. Data obtained with a 5 conditional mutant suggest that fks1 is not essential. In agreement,...

Aspergillus fumigatus is currently the major air-borne fungal pathogen as its asexual spores are distributed through the air. In severely immunocompromised patients, inhalation of these conidia can result in life-threatening infections. Invasive Aspergillosis, a major Aspergillus-associated disease, is associated with a high mortality reflecting sh...

Hyphae of filamentous Ascomycota consist of compartments that are connected via septal pores. To avoid a dramatic loss of cellular content after wounding, fungi developed mechanisms to occlude their septal pores. In most Pezizomycotina, so-called Woronin bodies are anchored in proximity to the pore. This is a prominent example for precise spatial p...

The mycelium of filamentous fungi is a network of interconnected hyphae. In most filamentous fungal species these hyphae are compartmentalized by internal cell walls. The cytoplasm of neighbouring compartments is connected via septal pores thus establishing a hyphal network that is able to act as a functional entity. Saccharomyces cerevisiae proved...

In filamentous fungi, the septal pore controls the exchange between neighbouring hyphal compartments. Woronin bodies are fungal-specific organelles that plug the pore in case of physical damage. The Hex protein is their major and essential component. Hex proteins of different size are predicted in the data base for pathogenic and non-pathogenic Asp...

Two-component signaling systems are widespread in bacteria, but also found in fungi. In this study, we have characterized TcsC, the only Group III two-component sensor kinase of Aspergillus fumigatus. TcsC is required for growth under hyperosmotic stress, but dispensable for normal growth, sporulation and conidial viability. A characteristic featur...

(A) Schematic drawing of the genomic tcsC gene and the deleted tcsC::hph/tk locus. Approximately 1 kb of the 5′ and 3′ regions of tcsC gene were used for construction of the deletion cassette. The positions of the primers employed for the PCR amplifications and the resulting PCR products (PCR 1-3) are indicated. (B) Equal amounts of genomic DNA of...

Resistance of the ΔtcsC mutant to iprodione and quintozene. The sensitivity to iprodione and quintozene was analyzed in drop dilution assays. AfS35 (top) and its ΔtcsC mutant (bottom) were spotted on plates without fungicides (panel A) or plates containing either 25 µg/ml quintozene (panel B) or 25 µg/ml iprodione (panel C). Pictures were taken aft...

Impact of fludioxonil during germination of A. fumigatus conidia. Conidia of A. fumigatus strain AfS35 were seeded on glass cover slips and incubated at 37°C in the presence of 1 µg/ml fludioxonil for 28 h (A, B) and 46 h (C to F). After 46 h the medium was replaced by fresh medium. Fungal cells fixed after another 15 h in the absence of fludioxoni...

Oligonucleotides used in this study. (DOC)

Despite the strong interest in the NK cell-mediated immunity toward malignant cells and viruses, there is a relative lack of data on the interplay between NK cells and filamentous fungi, especially Aspergillus fumigatus, which is the major cause of invasive aspergillosis. By studying the in vitro interaction between human NK cells and A. fumigatus,...

Galactofuranose is a hexose that is exclusively found in microbes and in particular in certain pathogenic species. In the mold Aspergillus fumigatus, it is the characteristic constituent of the cell wall component galactomannan. Detection of this carbohydrate is currently a widespread method used for diagnosis of systemic A. fumigatus infections. I...

Yersinia enterocolitica is a common cause of food borne gastrointestinal disease. After oral uptake, yersiniae invade Peyer's patches of the distal ileum. This is accomplished by the binding of the Yersinia invasin to β1 integrins on the apical surface of M cells which overlie follicle associated lymphoid tissue. The gut represents a barrier that s...

Sequence alignment of the Och1 proteins of Saccharomyces cerevisiae (ScOch1; YGL038C), Candida albicans (CaOch1; orf19.7391) and A. fumigatus (AfOch1; AFUA_5G08580). The Pfam domain PF04488 is indicated in red and the DXD motif is underlined. (DOC)

The presence of larger N-glycans in A. fumigatus requires Och1 expression and depends on culture conditions. Electropherograms of fluorescently labelled N-glycans enzymatically released from secreted glycoproteins of A. fumigatus parental strain AfS35, Δafoch1 and Δafoch1 + afoch1 strains grown either in Sabouraud broth or Aspergillus minimal media...

Probability of N-terminal signal sequences and membrane anchors of selected proteins of the Och1 family from A. fumigatus, S. cerevisiae, C. albicans and P. angusta. The sequences were analyzed using the SignalP 3.0 algorithm. The accession numbers of probabilities for a signal sequence or a membrane anchor is given in Panel A. A phylogenetic tree...

Oligonucleotides used in this study. (DOC)

Construction of the Δafoch4 mutant and its complementation. (A) Structure of the genomic afoch4 gene and the deleted afoch1::hph/tk locus. Approximately 1 kb of the 5′ and 3′ regions of afoch4 (gray boxed areas) were used for construction of the deletion cassette. The positions of the primers used for PCR amplifications and the resulting PCR produc...

Probability of N-terminal signal sequences and membrane anchors of Och1 proteins. The Och1 sequences of the indicated fungal species were analyzed using the SignalP 3.0 algorithm. The accession numbers of the analyzed sequences and their homology to the reference ScOch1 protein sequence are given. (DOC)

Probability of N-terminal signal sequences and membrane anchors for members of the Och1 family of A. fumigatus, S. cerevisiae, C. albicans, and P. augusta. The Och1 sequences of the indicated fungal species were analyzed using the SignalP 3.0 algorithm. The probabilities of N-terminal signal peptides and membrane anchors, as well as the homologies...

The mannosyltransferase Och1 is the key enzyme for synthesis of elaborated protein N-glycans in yeast. In filamentous fungi genes implicated in outer chain formation are present, but their function is unclear. In this study we have analyzed the Och1 protein of Aspergillus fumigatus. We provide first evidence that poly-mannosylated N-glycans exist i...

2779 NK cells are innate immune effector cells, which are well recognized for their role against cells transformed by malignant processes or by an intracellular infection. Although, there is increasing evidence of an interaction of NK cells also with extracellular pathogens, less is known about their interplay with moulds and especially with A. fum...

Neutrophil extracellular traps (NETs) represent a distinct mechanism to control and eliminate microbial infections. Our results show that conidia and germ tubes of the human pathogenic mold Aspergillus fumigatus are able to trigger the formation of NETs. Viable fungal cells are not essentially required for this host-pathogen interaction. Neutrophil...

Aspergillus fumigatus is currently the major air-borne fungal pathogen. It is able to cause several forms of disease in humans of which invasive aspergillosis is the most severe. The high mortality rate of this disease prompts increased efforts to disclose the basic principles of A. fumigatus pathogenicity. According to our current knowledge, A. fu...

Farnesol is known for inducing apoptosis in some fungi and mammalian cells. To evaluate its potential role as an antifungal agent, we studied its impact on the human pathogen Aspergillus fumigatus. We found that growth of A. fumigatus wild type is inhibited, but two cell wall mutants, Deltamnt1 andDeltaglfA, are much more susceptible to farnesol. T...

The cell wall integrity (CWI) pathway, best characterized in S. cerevisiae, is strikingly conserved in Aspergillus species. We analyzed the importance of AfMkk2, a CWI signaling kinase, for virulence and antifungal therapy in the human pathogen A. fumigatus. A mutant lacking AfMkk2 is less adherent to glass and plastic surfaces and shows increased...

GDP-mannose:inositol-phosphorylceramide (MIPC)-derived glycosphingolipids are important pathogen-associated molecular patterns (PAMP) of Candida albicans and according to recently published data also of Aspergillus fumigatus. MIPC transferases are essential for the synthesis of MIPC, but have so far been studied only in Saccharomyces cerevisiae and...

Invasive aspergillosis is a significant cause of morbidity and mortality in patients after stem cell transplantation, in solid organ transplant recipients, and in patients with hematological malignancies. The interactions between human immature dendritic cells (iDCs) and Aspergillus fumigatus antigens are widely uncharacterized. We analyzed the imm...

Aspergillus fumigatus is currently the major airborne fungal pathogen that menaces immunocompromised individuals. Germination of inhaled conidia is a hallmark of the early infection process, but little is known about the underlying mechanisms. The intention of our ongoing studies is the identification of A. fumigatus proteins that are differentiall...

Proteins entering the eukaryotic secretory pathway commonly are glycosylated. Important steps in this posttranslational modification are carried out by mannosyltransferases. In this study, we investigated the putative α-1,2-mannosyltransferase AfMnt1 of the human pathogenic mold Aspergillus fumigatus. AfMnt1 belongs to a family of enzymes that comp...