Signaling events driving Aspergillus fumigatus-induced eosinophil activation.

Allergic bronchopulmonary aspergillosis is an incurable disease caused by the environmental mold Aspergillus fumigatus. This hypersensitivity pneumonia is characterized by an inflammatory type 2 immune response, accompanied by influx of eosinophils into the lung. To investigate the mode of action of eosinophils and the signaling events triggered by A.

Magnetic Removal of Using Salivary Peptide-Functionalized SPIONs.

Purpose: Magnetic separation of microbes can be an effective tool for pathogen identification and diagnostic applications to reduce the time needed for sample preparation. After peptide functionalization of superparamagnetic iron oxide nanoparticles (SPIONs) with an appropriate interface, they can be used for the separation of sepsis-associated yeasts like . Due to their magnetic properties, the magnetic extraction of the particles in the presence of an external magnetic field ensures the accumulation of the targeted yeast.

Phosphatidylinositol 3-Kinase (PI3K) Orchestrates Aspergillus fumigatus-Induced Eosinophil Activation Independently of Canonical Toll-Like Receptor (TLR)/C-Type-Lectin Receptor (CLR) Signaling.

Eosinophilia is associated with various persisting inflammatory diseases and often coincides with chronic fungal infections or fungal allergy as in the case of allergic bronchopulmonary aspergillosis (ABPA). Here, we show that intranasal administration of live Aspergillus fumigatus conidia causes fatal lung damage in eosinophilic interleukin-5 (IL-5)-transgenic mice. To further investigate the activation of eosinophils by A.

Transcriptional response of to copper and the role of the Cu chaperones.

is the leading cause of life-threatening invasive mold infections in immunocompromised individuals. This ubiquitous saprophyte possesses several natural attributes allowing it to evade the immune system, including the ability to withstand high toxic Cu concentrations within the phagosomes of macrophages and neutrophils. We previously established that at high levels, Cu binds and activates the transcription factor AceA, which upregulates the expression of the Cu exporter CrpA to expel excess Cu.

Direct Visualization of Fungal Burden in Filamentous Fungus-Infected Silkworms.

Invasive fungal infections (IFIs) are difficult to diagnose and to treat and, despite several available antifungal drugs, cause high mortality rates. In the past decades, the incidence of IFIs has continuously increased. More recently, SARS-CoV-2-associated lethal IFIs have been reported worldwide in critically ill patients.

The master regulator MAT1-1-1 of fungal mating binds to its targets via a conserved motif in the human pathogen Aspergillus fumigatus.

Mating-type transcription factors are master regulators of sexually related signal transduction pathways in fungi; however, their recognition of specific DNA sequences from target genes is widely undetermined. Here, we identified and characterized the DNA-binding sequence of the MAT1-1-1 alpha-box domain transcription factor from the human pathogen Aspergillus fumigatus. In order to explore MAT1-1-1 DNA-binding targets, we used the previously reported MAT1-1-1 binding motif from Penicillium chrysogenum, in a bioinformatics approach.

The infectious propagules of Aspergillus fumigatus are coated with antimicrobial peptides.

Fungal spores are unique cells that mediate dispersal and survival in the environment. For pathogenic fungi encountering a susceptible host, these specialised structures may serve as infectious particles. The main causative agent of the opportunistic disease aspergillosis, Aspergillus fumigatus, produces asexual spores, the conidia, that become dissipated by air flows or water currents but also serve as propagules to infect a susceptible host.

On the lineage of Aspergillus fumigatus isolates in common laboratory use.

Unlabelled: The origin of isolates routinely used by the community of Aspergillus fumigatus researchers is periodically a matter of intense discussion at our centre, as the construction of recombinant isolates have sometimes followed convoluted routes, the documentation describing their lineages is fragmented, and the nomenclature is confusing. As an aide memoir, not least for our own benefit, we submit the following account and tabulated list of strains (Table 1) in an effort to collate all of the relevant information in a single, easily accessible document. To maximise the accuracy of this record we have consulted widely amongst the community of Medical Mycologists using these strains.

The Essential Thioredoxin Reductase of the Human Pathogenic Mold Is a Promising Antifungal Target.

The identification of cellular targets for antifungal compounds is a cornerstone for the development of novel antimycotics, for which a significant need exists due to increasing numbers of susceptible patients, emerging pathogens, and evolving resistance. For the human pathogenic mold , the causative agent of the opportunistic disease aspergillosis, only a limited number of established targets and corresponding drugs are available. Among several targets that were postulated from a variety of experimental approaches, the conserved thioredoxin reductase (TrxR) activity encoded by the gene was assessed in this study.

Th2 cells promote eosinophil-independent pathology in a murine model of allergic bronchopulmonary aspergillosis.

Repeated inhalation of airborne conidia derived from the fungus Aspergillus fumigatus (Af) can lead to a severe eosinophil-dominated inflammatory condition of the lung termed allergic bronchopulmonary aspergillosis (ABPA). ABPA affects about 5 million individuals worldwide and the mechanisms regulating lung pathology in ABPA are poorly understood. Here, we used a mouse model of ABPA to investigate the role of eosinophils and T cell-derived IL-4/IL-13 for induction of allergic lung inflammation.

Three-Dimensional Light Sheet Fluorescence Microscopy of Lungs To Dissect Local Host Immune-Aspergillus fumigatus Interactions.

is an opportunistic fungal pathogen that can cause life-threatening invasive lung infections in immunodeficient patients. The cellular and molecular processes of infection during onset, establishment, and progression of infections are highly complex and depend on both fungal attributes and the immune status of the host. Therefore, preclinical animal models are of paramount importance to investigate and gain better insight into the infection process.

Aspergillus fumigatus Spores Are Not Able to Penetrate Silicone Breast Implant Shells.

Introduction: Bacterial contamination is hypothesized to be one reason for the development of capsular contracture after alloplastic breast reconstruction using silicone breast implants. The role of fungal colonization or infection in this context as well as the question if microorganisms can penetrate the shell of silicone breast implants remains an unresolved question to date. Therefore, the aim of this study was to assess whether fungal spores are able to penetrate the shell of silicone implants.

-Derived Volatile Sulfur Compounds Promote Distal Growth and a Synergistic Pathogen-Pathogen Interaction That Increases Pathogenicity in Co-infection.

Pathogen-pathogen interactions in polymicrobial infections are known to directly impact, often to worsen, disease outcomes. For example, co-infection with and , respectively the most common bacterial and fungal pathogens isolated from cystic fibrosis (CF) airways, leads to a worsened prognosis. Recent studies of microbial cross-talk demonstrated that -derived volatile sulfur compounds (VSCs) can promote growth .

Impairing fluoride export of Aspergillus fumigatus mitigates its voriconazole resistance.

Fungi have evolved specific export activities to balance intracellular levels of the toxic ion fluoride, while the first-line antimycotic voriconazole contains fluorine. This study aimed to explore whether impaired fluoride export might result in altered susceptibilities of the human pathogenic mould Aspergillus fumigatus towards this antifungal compound. Functional characterization of the putative fluoride exporter in A.

Proteome Analysis Reveals the Conidial Surface Protein CcpA Essential for Virulence of the Pathogenic Fungus .

is a common airborne fungal pathogen of humans and a significant source of mortality in immunocompromised individuals. Here, we provide the most extensive cell wall proteome profiling to date of resting conidia, the fungal morphotype pertinent to first contact with the host. Using liquid chromatography-tandem mass spectrometry (LC-MS/MS), we identified proteins within the conidial cell wall by hydrogen-fluoride (HF)-pyridine extraction and proteins exposed on the surface using a trypsin-shaving approach.

Mating-type factor-specific regulation of the fumagillin/pseurotin secondary metabolite supercluster in Aspergillus fumigatus.

In the human pathogenic mold Aspergillus fumigatus, sexual identity is determined by the mating-type idiomorphs MAT1-1 and MAT1-2 residing at the MAT locus. Upon crossing of compatible partners, a heterothallic mating is executed to eventually form cleistothecia that contain recombinant ascospores. Given that the MAT1 gene products are DNA binding master regulators that govern this complex developmental process, we monitored the MAT1-driven transcriptomes of A.

Murine eosinophil development and allergic lung eosinophilia are largely dependent on the signaling adaptor GRB2.

Eosinophils are innate effector cells associated with allergic inflammation. Their development and survival is largely dependent on IL-5 and the common beta chain (β ) of the IL-5 receptor that serves as docking site for several proteins that mediate down-stream signaling cascades including JAK/STAT, PI3 kinase, NFκB, and RAS-MAP kinase pathways. The relative contribution of these signaling pathways for eosinophil development and homeostasis in vivo are poorly understood.

Current challenges of research on filamentous fungi in relation to human welfare and a sustainable bio-economy: a white paper.

The EUROFUNG network is a virtual centre of multidisciplinary expertise in the field of fungal biotechnology. The first academic-industry Think Tank was hosted by EUROFUNG to summarise the state of the art and future challenges in fungal biology and biotechnology in the coming decade. Currently, fungal cell factories are important for bulk manufacturing of organic acids, proteins, enzymes, secondary metabolites and active pharmaceutical ingredients in white and red biotechnology.

The novel Aspergillus fumigatus MAT1-2-4 mating-type gene is required for mating and cleistothecia formation.

Sexual propagation accompanied by recombination and the formation of spore-containing fruiting bodies is a cornerstone of fungal genetics and biology. In the human pathogen Aspergillus fumigatus sexual identity has previously been shown to be determined by MAT1-1-1 or MAT1-2-1 genes which act as transcriptional regulators and are present within idiomorphs found at the MAT locus. We here report the identification and first characterization of a further novel gene, termed MAT1-2-4, that is present in the MAT1-2 idiomorph of A.

When green and red mycology meet: Impressions from an interdisciplinary forum on virulence mechanisms of phyto- and human-pathogenic fungi.

Fungal infections pose a constant threat to plants and humans, but detailed knowledge about pathogenesis, immunity, or virulence is rather scarce. Due to the fact that a certain overlap in the armoury of infection exists between plant- and human-pathogenic fungi, an interdisciplinary forum was held in October 2016 at the Institute for Clinical Microbiology, Immunology and Hygiene in Erlangen under the organisational umbrella from two special interest groups of German microbial societies. Scientific exchange and intense discussion of this timely topic was fostered by bringing together renowned experts in their respective fields to present their thoughts and recent findings in the course of a plenary lecture and six themed sessions, accompanied by oral and poster contributions of young researchers.

Influence of Platelet-rich Plasma on the immune response of human monocyte-derived dendritic cells and macrophages stimulated with Aspergillus fumigatus.

Dendritic cells (DCs) and macrophages (MΦ) are critical for protection against pathogenic fungi including Aspergillus fumigatus. To analyze the role of platelets in the innate immune response, human DCs and MΦs were challenged with A. fumigatus in presence or absence of human platelet rich plasma (PRP).