1,782 results match your criteria: "Leibniz Institute for Natural Product[Affiliation]"

Variations in candidalysin amino acid sequence influence toxicity and host responses.

mBio

August 2024

Centre for Host-Microbiome Interactions, Faculty of Dentistry, Oral & Craniofacial Sciences, King's College London, London, United Kingdom.

Article Synopsis
  • Candidalysin is a toxin produced by Candida species, playing a significant role in causing mucosal infections and damaging host tissues, which exacerbates diseases and immune responses.* -
  • Recent studies discovered multiple variants of candidalysin in different Candida isolates, indicating a wider genetic diversity and potential differences in how they affect host cells.* -
  • Experiments showed that these candidalysin variants cause varying levels of cellular damage and biological responses in epithelial cells, highlighting their importance in understanding fungal infections.*
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a novel dimorphic species resembling in a clinical sample: questions on ecological strategy.

mBio

August 2024

Microbiology Service, Department of Laboratory Medicine, Clinical Center, National Institutes of Health, Bethesda, Maryland, USA.

Article Synopsis
  • Dimorphism is a phenomenon where certain fungi can switch between yeast and filamentous forms depending on temperature, which is explored in the study of a new mucoralean fungus isolated from a patient with Burkitt lymphoma.
  • The fungus shows significant changes in shape and structure at body temperature, resembling traditional yeast forms but still having unique features that can help differentiate it from other similar fungi in clinical settings.
  • Accurate and timely diagnosis is crucial for managing mucormycosis, as different fungal species have varied responses to antifungal treatments, highlighting the need to recognize these dimorphic transitions to improve patient outcomes.
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an opportunistic fungal pathogen, produces the quorum-sensing molecule farnesol, which we have shown alters the transcriptional response and phenotype of human monocyte-derived dendritic cells (DCs), including their cytokine secretion and ability to prime T cells. This is partially dependent on the nuclear receptor peroxisome proliferator-activated receptor gamma (PPAR-γ), which has numerous ligands, including the sphingolipid metabolite sphingosine 1-phosphate. Sphingolipids are a vital component of membranes that affect membrane protein arrangement and phagocytosis of by DCs.

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The candidate phyla radiation (CPR) represents a distinct monophyletic clade and constitutes a major portion of the tree of life. Extensive efforts have focused on deciphering the functional diversity of its members, primarily using sequencing-based techniques. However, cultivation success remains scarce, presenting a significant challenge, particularly in CPR-dominated groundwater microbiomes characterized by low biomass.

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Biosynthesis and recruitment of reactive amino acids in nonribosomal peptide assembly lines.

Curr Opin Chem Biol

August 2024

Department of Biomolecular Chemistry, Leibniz Institute for Natural Product Research and Infection Biology (HKI), Beutenbergstr. 11a, 07745 Jena, Germany; Institute of Microbiology, Faculty of Biological Sciences, Friedrich Schiller University Jena, 07743 Jena, Germany. Electronic address:

Reactive amino acid side chains play important roles in the binding of peptides to specific targets. In addition, their reactivity enables selective peptide conjugation and functionalization for pharmaceutical purposes. Diverse reactive amino acids are incorporated into nonribosomal peptides, which serve as a source for drug candidates.

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Bioethanol is a sustainable energy alternative and can contribute to global greenhouse-gas emission reductions by over 60%. Its industrial production faces various bottlenecks, including sub-optimal efficiency resulting from bacteria. Broad-spectrum removal of these contaminants results in negligible gains, suggesting that the process is shaped by ecological interactions within the microbial community.

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Invasive aspergillosis causes significant morbidity and mortality in immunocompromised patients. Natural killer (NK) cells are pivotal for antifungal defense. Thus far, CD56 is the only known pathogen recognition receptor on NK cells triggering potent antifungal activity against Aspergillus fumigatus.

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Functional analysis of the Aspergillus fumigatus kinome identifies a druggable DYRK kinase that regulates septal plugging.

Nat Commun

June 2024

Manchester Fungal Infection Group, Division of Evolution, Infection and Genomic Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.

Article Synopsis
  • * Researchers created a library of 111 genetically modified Aspergillus fumigatus mutants to identify important antifungal targets, discovering that a specific kinase, YakA, is crucial for regulating susceptibility to azoles and pathogenicity.
  • * The study found that inhibiting YakA not only weakens the fungus's ability to grow and invade tissues but also enhances the effectiveness of azoles when combined with a compound (1-ECBC), suggesting a potential avenue for improving treatment.
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Fungi constitute the Earth's second most diverse kingdom, however only a small percentage of these have been thoroughly examined and categorized for their secondary metabolites, which still limits our understanding of the ecological chemical and pharmacological potential of fungi. In this study, we explored members of the co-evolved termite-associated fungal genus Xylaria and identified a family of highly oxygenated polyketide-terpene hybrid natural products using an MS/MS molecular networking-based dereplication approach. Overall, we isolated six no yet reported xylasporin derivatives, of which xylasporin A (1) features a rare cyclic-carbonate moiety.

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Long versus short course anti-microbial therapy of uncomplicated Staphylococcus aureus bacteraemia: a systematic review.

Clin Microbiol Infect

October 2024

Institute for Infectious Disease and Infection Control, Jena University Hospital, Friedrich-Schiller-University, Jena, Germany; Leibniz Institute for Natural Product Research and Infection Biology, Hans-Knöll Institute, Jena, Germany. Electronic address:

Background: Current guidelines recommend at least 2 weeks duration of antibiotic therapy (DOT) for patients with uncomplicated Staphylococcus aureus bacteraemia (SAB) but the evidence for this recommendation is unclear.

Objectives: To perform a systematic literature review assessing current evidence for recommended DOT for patients with SAB.

Methods: The following are the methods used for this study.

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Insights into invasive fungal infection diagnostic and treatment capacities in tertiary care centres of Germany.

JAC Antimicrob Resist

June 2024

Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, University Hospital Cologne, Institute of Translational Research, Herderstraße 52, 50931 Cologne, Germany.

Article Synopsis
  • - The rising rate of invasive fungal infections (IFIs) in Germany poses a serious health issue, particularly for immunocompromised patients, and is complicated by diagnostic challenges and increasing antifungal resistance.
  • - A survey of 58 hospitals revealed that while many facilities have adequate diagnostic tools, there are significant differences in resources, particularly for high-risk patients, with specialized hospitals offering better access to necessary services.
  • - The study emphasizes the need for improved diagnostic and treatment practices for IFIs to enhance patient outcomes, highlighting the importance of ongoing research and collaboration in this field.
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Quantitative imaging in life sciences has evolved into a powerful approach combining advanced microscopy acquisition and automated analysis of image data. The focus of the present study is on the imaging-based evaluation of the posterior cricoarytenoid muscle (PCA) influenced by long-term functional electrical stimulation (FES), which may assist the inspiration of patients with bilateral vocal fold paresis. To this end, muscle cross-sections of the PCA of sheep were examined by quantitative image analysis.

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The impact of high-salt diet on asthma in humans and mice: Effect on specific T-cell signatures and microbiome.

Allergy

July 2024

Center of Allergy & Environment (ZAUM), Technical University of Munich (TUM) and Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.

Article Synopsis
  • The study investigates the relationship between high dietary salt intake and asthma incidence, finding a direct association among females but not males in human subjects.
  • Using mouse models, researchers observed that a high-salt diet worsened allergic airway inflammation, impacting immune responses and stress gene expression.
  • The findings indicated significant changes in the microbiome of both gut and lungs due to high salt consumption, suggesting a complex interaction between diet, immune response, and asthma development.
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6-Thioguanine (6TG) is a clinically used antitumor agent that was rationally designed as a DNA-targeting antimetabolite, but it also occurs naturally. 6TG is a critical virulence factor produced by Erwinia amylovorans, a notorious plant pathogen that causes fire blight of pome fruit trees. The biosynthesis of the rare thioamide metabolite involves an adenylating enzyme (YcfA) and a sulfur-mobilizing enzyme (YcfC), but the mechanism of sulfur transfer and putative intermediates have remained elusive.

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Unlabelled: Amoebae are environmental predators feeding on bacteria, fungi, and other eukaryotic microbes. Predatory interactions alter microbial communities and impose selective pressure toward phagocytic resistance or escape which may, in turn, foster virulence attributes. The ubiquitous fungivorous amoeba has a wide prey spectrum in the fungal kingdom but discriminates against members of the clade, such as and .

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Background: Enhancing our understanding of the underlying influences of medical interventions on the microbiome, resistome and mycobiome of preterm born infants holds significant potential for advancing infection prevention and treatment strategies. We conducted a prospective quasi-intervention study to better understand how antibiotics, and probiotics, and other medical factors influence the gut development of preterm infants. A controlled neonatal mice model was conducted in parallel, designed to closely reflect and predict exposures.

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Isotope labeled 3D-Raman confocal imaging and atomic force microscopy study on epithelial cells interacting with the fungus Candida albicans.

Nanomedicine

July 2024

Leibniz Institute of Photonic Technology, Albert-Einstein-Straße 9, 07745 Jena, Germany; Institute for Physical Chemistry and Abbe Center of Photonics, Friedrich Schiller University Jena, Helmholtzweg 4, 07743 Jena, Germany. Electronic address:

The human pathogenic fungus Candida albicans damages epithelial cells during superficial infections. Here we use three-dimensional-sequential-confocal Raman spectroscopic imaging and atomic force microscopy to investigate the interaction of C. albicans wild type cells, the secreted C.

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Direct α-Hydroxy Acid Loading onto a Bacterial Thiotemplate Assembly Line via a Multienzyme Gateway.

Angew Chem Int Ed Engl

July 2024

Department of Biomolecular Chemistry, Leibniz Institute for Natural Product, Research and Infection Biology (HKI), Beutenbergstraße 11a, 07745, Jena, Germany.

Various nonribosomal peptide synthetases (NRPSs) create structural and functional diversity by incorporating α-hydroxy acids into peptide backbones. Trigonic acid, an unusual cyclopropanol-substituted hydroxy acid, is the source of the molecular warhead of malleicyprol, a critical virulence factor of human and animal pathogens of the Burkholderia pseudomallei (BP) group. The process of selecting and loading this building block remained enigmatic as the NRPS module designated for this task is incomplete.

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Cervimycins A-D are bis-glycosylated polyketide antibiotics produced by HKI 0179 with bactericidal activity against Gram-positive bacteria. In this study, cervimycin C (CmC) treatment caused a spaghetti-like phenotype in 168, with elongated curved cells, which stayed joined after cell division, and exhibited a chromosome segregation defect, resulting in ghost cells without DNA. Electron microscopy of CmC-treated (3 × MIC) revealed swollen cells, misshapen septa, cell wall thickening, and a rough cell wall surface.

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A wide variety of treatments have been developed to improve respiratory function and quality of life in patients with bilateral vocal fold paresis (BVFP). One experimental method is the electrical activation of the posterior cricoarytenoid (PCA) muscle with a laryngeal pacemaker (LP) to open the vocal folds. We used an ovine (sheep) model of unilateral VFP to study the long-term effects of functional electrical stimulation on the PCA muscles.

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Article Synopsis
  • * Factor H (FH) regulates this system, preventing damage to the body's own cells and has been found to interact with human influenza A viruses (IAVs) through the virus's surface protein, haemagglutinin (HA).
  • * The study shows that FH can affect the entry of certain IAV strains into cells, with varying impacts on viral replication, clearly demonstrating that the interactions between FH and IAV depend on the specific strain involved.
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The endosymbiosis between the pathogenic fungus Rhizopus microsporus and the toxin-producing bacterium Mycetohabitans rhizoxinica represents a unique example of host control by an endosymbiont. Fungal sporulation strictly depends on the presence of endosymbionts as well as bacterially produced secondary metabolites. However, an influence of primary metabolites on host control remained unexplored.

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Background: Although Basidiomycota produce pharmaceutically and ecologically relevant natural products, knowledge of how they coordinate their primary and secondary metabolism is virtually non-existent. Upon transition from vegetative mycelium to carpophore formation, mushrooms of the genus Psilocybe use L-tryptophan to supply the biosynthesis of the psychedelic tryptamine alkaloid psilocybin with the scaffold, leading to a strongly increased demand for this particular amino acid as this alkaloid may account for up to 2% of the dry mass. Using Psilocybe mexicana as our model and relying on genetic, transcriptomic, and biochemical methods, this study investigated if L-tryptophan biosynthesis and degradation in P.

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Genome-Driven Discovery of Hygrocins in .

J Nat Prod

May 2024

Department of Biotechnology and Biomedicine, Technical University of Denmark, Søltofts Plads 221, 2800 Kgs. Lyngby, Denmark.

Article Synopsis
  • * Researchers fermented IMET 43975 to isolate five known and four new ansamycin analogues, including new compounds called hygrocins.
  • * The structural analysis of these ansamycins was conducted using advanced techniques, and a specific enzyme involved in their formation was confirmed through CRISPR base editing, enhancing our understanding of their diversity.
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