ProcCluster® and procaine hydrochloride inhibit the growth of species and exert antimicrobial properties during coinfection with influenza A viruses and .

Introduction: Influenza-associated pulmonary aspergillosis is associated with high mortality rates and limited treatment options. The current standard practice involves treating each pathogen separately. However, the use of antifungal drugs can lead to serious side effects, and the presence of triazole-resistant strains can complicate antifungal therapy.

Aspergillus fumigatus-derived gliotoxin impacts innate immune cell activation through modulating lipid mediator production in macrophages.

Gliotoxin (GT), a secondary metabolite and virulence factor of the fungal pathogen Aspergillus fumigatus, suppresses innate immunity and supports the suppression of host immune responses. Recently, we revealed that GT blocks the formation of the chemotactic lipid mediator leukotriene (LT)B in activated human neutrophils and monocytes, and in rodents in vivo, by directly inhibiting LTA hydrolase. Here, we elucidated the impact of GT on LTB biosynthesis and the entire lipid mediator networks in human M1- and M2-like monocyte-derived macrophages (MDMs) and in human tissue-resident alveolar macrophages.

The influenza A virus promotes fungal growth of Aspergillus fumigatus via direct interaction in vitro.

Seasonal influenza A virus (IAV) infections still pose a major burden for public health worldwide. Severe disease progression or even death is often related to superinfections of the virus and a secondary bacterial pathogen. However, fungi, especially Aspergillus fumigatus, are also frequently diagnosed during IAV infection.

A phylogenetic approach to explore the conidial surface-associated proteome and its role in pathogenesis.

, an important pulmonary fungal pathogen causing several diseases collectively called aspergillosis, relies on asexual spores (conidia) for initiating host infection. Here, we used a phylogenomic approach to compare proteins in the conidial surface of , two closely related non-pathogenic species, and , and the cryptic pathogen . After identifying 62 proteins uniquely expressed on the conidial surface, we assessed null mutants for 42 genes encoding conidial proteins.

A phylogenetic approach to explore the conidial surface-associated proteome and its role in pathogenesis.

, an important pulmonary fungal pathogen causing several diseases collectively called aspergillosis, relies on asexual spores or conidia for initiating host infection. Here, we used a phylogenomic approach to compare proteins in the conidial surface of , two closely related non-pathogenic species, and , and the cryptic pathogen . After identifying 62 proteins uniquely expressed on the conidial surface, we deleted 42 genes encoding conidial proteins.

Aspergillus fumigatus hijacks human p11 to redirect fungal-containing phagosomes to non-degradative pathway.

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 is a critical factor for this decision. The HscA protein present on the conidial surface of the human-pathogenic fungus Aspergillus fumigatus anchors p11 on conidia-containing phagosomes (PSs), excludes the PS maturation mediator Rab7, and triggers binding of exocytosis mediators Rab11 and Sec15.

The Lipid Raft-Associated Protein Stomatin Is Required for Accumulation of Dectin-1 in the Phagosomal Membrane and for Full Activity of Macrophages against Aspergillus fumigatus.

Alveolar macrophages belong to the first line of defense against inhaled conidia of the human-pathogenic fungus Aspergillus fumigatus. In lung alveoli, they contribute to phagocytosis and elimination of conidia. As a counterdefense, conidia have a gray-green pigment that enables them to survive in phagosomes of macrophages for some time.

Targeting of phagolysosomes containing conidia of the fungus Aspergillus fumigatus with polymeric particles.

Conidia of the airborne human-pathogenic fungus Aspergillus fumigatus are inhaled by humans. In the lung, they are phagocytosed by alveolar macrophages and intracellularly processed. In macrophages, however, conidia can interfere with the maturation of phagolysosomes to avoid their elimination.

Prediction and validation of host-pathogen interactions by a versatile inference approach using as a case study.

Biological networks are characterized by diverse interactions and dynamics in time and space. Many regulatory modules operate in parallel and are interconnected with each other. Some pathways are functionally known and annotated accordingly, e.

Peroxiredoxin Asp f3 Is Essential for Aspergillus fumigatus To Overcome Iron Limitation during Infection.

Aspergillus fumigatus is an important fungal pathogen that causes allergic reactions but also life-threatening infections. One of the most abundant A. fumigatus proteins is Asp f3.

CRISPR-Cas9-Based Discovery of the Verrucosidin Biosynthesis Gene Cluster in .

, commonly found on food matrices, is a mycotoxigenic species able to produce a neurotoxin called verrucosidin. This methylated α-pyrone polyketide inhibits oxidative phosphorylation in mitochondria and thereby causes neurological diseases. Despite the importance of verrucosidin as a toxin, its biosynthetic genes have not been characterized yet.

Discovery of fungal surface NADases predominantly present in pathogenic species.

Nicotinamide adenine dinucleotide (NAD) is a key molecule in cellular bioenergetics and signalling. Various bacterial pathogens release NADase enzymes into the host cell that deplete the host's NAD pool, thereby causing rapid cell death. Here, we report the identification of NADases on the surface of fungi such as the pathogen Aspergillus fumigatus and the saprophyte Neurospora crassa.

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.

N-Heterocyclization in Gliotoxin Biosynthesis is Catalyzed by a Distinct Cytochrome P450 Monooxygenase.

Gliotoxin and related epidithiodiketopiperazines (ETP) from diverse fungi feature highly functionalized hydroindole scaffolds with an array of medicinally and ecologically relevant activities. Mutation analysis, heterologous reconstitution, and biotransformation experiments revealed that a cytochrome P450 monooxygenase (GliF) from the human-pathogenic fungus Aspergillus fumigatus plays a key role in the formation of the complex heterocycle. In vitro assays using a biosynthetic precursor from a blocked mutant showed that GliF is specific to ETPs and catalyzes an unprecedented heterocyclization reaction that cannot be emulated with current synthetic methods.

Flotillin-Dependent Membrane Microdomains Are Required for Functional Phagolysosomes against Fungal Infections.

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 membranes of macrophages and depend on flotillins. Genetic deletion of flotillins demonstrates that the assembly of both major defense complexes vATPase and NADPH oxidase requires membrane microdomains.

The Pheromone Module SteC-MkkB-MpkB-SteD-HamE Regulates Development, Stress Responses and Secondary Metabolism in .

In order for eukaryotes to efficiently detect and respond to environmental stimuli, a myriad of protein signaling pathways are utilized. An example of highly conserved signaling pathways in eukaryotes are the mitogen-activated protein kinase (MAPK) pathways. In fungi, MAPK pathways have been shown to regulate a diverse array of biological processes, such as asexual and sexual development, stress responses and the production of secondary metabolites (SMs).

Caspofungin Functionalized Polymethacrylates with Antifungal Properties.

We describe the synthesis of hydrophilic poly(poly(ethylene glycol) methyl ether methacrylate) (PmPEGMA) and hydrophobic poly(methyl methacrylate) (PMMA) caspofungin conjugates by a post-polymerization modification of copolymers containing 10 mol % pentafluorophenyl methacrylate (PFPMA), which were obtained via reversible addition-fragmentation chain transfer copolymerization. The coupling of the clinically used antifungal caspofungin was confirmed and quantified in detail by a combination of H-, F- and diffusion-ordered NMR spectroscopy, UV-vis spectroscopy, and size exclusion chromatography. The trifunctional amine-containing antifungal was attached via several amide bonds to the hydrophobic PMMA, but sterical hindrance induced by the mPEGMA side chains prohibited intramolecular double functionalization.

Towards Raman spectroscopy of urine as screening tool.

For the screening purposes urine is an especially attractive biofluid, since it offers easy and noninvasive sample collection and provides a snapshot of the whole metabolic status of the organism, which may change under different pathological conditions. Raman spectroscopy (RS) has the potential to monitor these changes and utilize them for disease diagnostics. The current study utilizes mouse models aiming to compare the feasibility of the urine based RS combined with chemometrics for diagnosing kidney diseases directly influencing urine composition and respiratory tract diseases having no direct connection to urine formation.

High-Throughput Gene Replacement in Aspergillus fumigatus.

Aspergillus fumigatus is a human pathogen and the principal etiologic agent of invasive and chronic aspergillosis leading to several hundreds of thousands of deaths every year. Very few antifungals are available to treat infections caused by A. fumigatus, and resistance is developing to those we have.

Mitogen-Activated Protein Kinase Cross-Talk Interaction Modulates the Production of Melanins in Aspergillus fumigatus.

The pathogenic fungus is able to adapt to extremely variable environmental conditions. The genome contains four genes coding for mitogen-activated protein kinases (MAPKs), which are important regulatory knots involved in diverse cellular responses. From a clinical perspective, MAPK activity has been connected to salvage pathways, which can determine the failure of effective treatment of invasive mycoses using antifungal drugs.

Gliotoxin from Aspergillus fumigatus Abrogates Leukotriene B Formation through Inhibition of Leukotriene A Hydrolase.

The epidithiodioxopiperazine gliotoxin is a virulence factor of Aspergillus fumigatus, the most important airborne fungal pathogen of humans. Gliotoxin suppresses innate immunity in invasive aspergillosis, particularly by compromising neutrophils, but the underlying molecular mechanisms remain elusive. Neutrophils are the first responders among innate immune cells recruited to sites of infection by the chemoattractant leukotriene (LT)B that is biosynthesized by 5-lipoxygenase and LTA hydrolase (LTAH).