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.

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.

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.

Systematic Identification of Anti-Fungal Drug Targets by a Metabolic Network Approach.

New antimycotic drugs are challenging to find, as potential target proteins may have close human orthologs. We here focus on identifying metabolic targets that are critical for fungal growth and have minimal similarity to targets among human proteins. We compare and combine here: (I) direct metabolic network modeling using elementary mode analysis and flux estimates approximations using expression data, (II) targeting metabolic genes by transcriptome analysis of condition-specific highly expressed enzymes, and (III) analysis of enzyme structure, enzyme interconnectedness ("hubs"), and identification of pathogen-specific enzymes using orthology relations.

Exploration of Sulfur Assimilation of Aspergillus fumigatus Reveals Biosynthesis of Sulfur-Containing Amino Acids as a Virulence Determinant.

Fungal infections are of major relevance due to the increased numbers of immunocompromised patients, frequently delayed diagnosis, and limited therapeutics. To date, the growth and nutritional requirements of fungi during infection, which are relevant for invasion of the host, are poorly understood. This is particularly true for invasive pulmonary aspergillosis, as so far, sources of (macro)elements that are exploited during infection have been identified to only a limited extent.

Mutant characterization and in vivo conditional repression identify aromatic amino acid biosynthesis to be essential for Aspergillus fumigatus virulence.

Pathogenicity of the saprobe Aspergillus fumigatus strictly depends on nutrient acquisition during infection, as fungal growth determines colonisation and invasion of a susceptible host. Primary metabolism has to be considered as a valid target for antimycotic therapy, based on the fact that several fungal anabolic pathways are not conserved in higher eukaryotes. To test whether fungal proliferation during invasive aspergillosis relies on endogenous biosynthesis of aromatic amino acids, defined auxotrophic mutants of A.

Endocytosis of GABA(C) receptors depends on subunit composition and is regulated by protein kinase C-ζ and protein phosphatase 1.

Neuronal excitability depends on the surface concentration of neurotransmitter receptors. Type C gamma-aminobutyric acid receptors (GABA(C)R) are composed of ρ subunits that are highly expressed in the retina. Molecular mechanisms that guide the surface concentration of this receptor type are largely unknown.