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227 results on '"MÜSKEN, MATHIAS"'

1. Klebsiella oxytoca inhibits Salmonella infection through multiple microbiota-context-dependent mechanisms

Author

Osbelt, Lisa, Almási, Éva d. H., Wende, Marie, Kienesberger, Sabine, Voltz, Alexander, Lesker, Till R., Muthukumarasamy, Uthayakumar, Knischewski, Nele, Nordmann, Elke, Bielecka, Agata A., Giralt-Zúñiga, María, Kaganovitch, Eugen, Kühne, Caroline, Baier, Claas, Pietsch, Michael, Müsken, Mathias, Greweling-Pils, Marina C., Breinbauer, Rolf, Flieger, Antje, Schlüter, Dirk, Müller, Rolf, Erhardt, Marc, Zechner, Ellen L., and Strowig, Till

Published
2024
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2. Host macrocyclic acylcarnitines mediate symbiotic interactions between frogs and their skin microbiome.

Author

Brunetti, Andrés, Lyra, Mariana, Bauermeister, Anelize, Bunk, Boyke, Boedeker, Christian, Müsken, Mathias, Neto, Fausto, Mendonça, Jacqueline, Caraballo-Rodríguez, Andrés, Melo, Weilan, Pupo, Mônica, Haddad, Célio, Cabrera, Gabriela, Overmann, Jörg, and Lopes, Norberto

Subjects
Biological sciences, Metabolomics, Microbial metabolism, Microbiology, Omics
Abstract

The host-microbiome associations occurring on the skin of vertebrates significantly influence hosts health. However, the factors mediating their interactions remain largely unknown. Herein, we used integrated technical and ecological frameworks to investigate the skin metabolites sustaining a beneficial symbiosis between tree frogs and bacteria. We characterize macrocyclic acylcarnitines as the major metabolites secreted by the frogs skin and trace their origin to an enzymatic unbalance of carnitine palmitoyltransferases. We found that these compounds colocalize with bacteria on the skin surface and are mostly represented by members of the Pseudomonas community. We showed that Pseudomonas sp. MPFS isolated from frogs skin can exploit acylcarnitines as its sole carbon and nitrogen source, and this metabolic capability is widespread in Pseudomonas. We summarize frogs multiple mechanisms to filter environmental bacteria and highlight that acylcarnitines likely evolved for another function but were co-opted to provide nutritional benefits to the symbionts.

Published
2023

7. The natural product chlorotonil A preserves colonization resistance and prevents relapsing Clostridioides difficile infection

Author

Bublitz, Arne, Brauer, Madita, Wagner, Stefanie, Hofer, Walter, Müsken, Mathias, Deschner, Felix, Lesker, Till R., Neumann-Schaal, Meina, Paul, Lena-Sophie, Nübel, Ulrich, Bartel, Jürgen, Kany, Andreas M., Zühlke, Daniela, Bernecker, Steffen, Jansen, Rolf, Sievers, Susanne, Riedel, Katharina, Herrmann, Jennifer, Müller, Rolf, Fuchs, Thilo M., and Strowig, Till

Published
2023
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8. An autonomous plasmid as an inovirus phage satellite

Author

Schmid, Nicole, primary, Brandt, David, additional, Walasek, Claudia, additional, Rolland, Clara, additional, Wittmann, Johannes, additional, Fischer, Dorian, additional, Müsken, Mathias, additional, Kalinowski, Jörn, additional, and Thormann, Kai, additional

Published
2024
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13. Screening Privileged Alkyl Guanidinium Motifs under Host-Mimicking Conditions Reveals a Novel Antibiotic with an Unconventional Mode of Action

Author

Schum, Dominik, Elsen, Franziska A. V., Ruddell, Stuart, Schorpp, Kenji, Junca, Howard, Müsken, Mathias, Chen, Shu-Yu, Fiedler, Michaela K., Pickl, Thomas, Pieper, Dietmar H., Hadian, Kamyar, Zacharias, Martin, and Sieber, Stephan A.

Abstract

Screening large molecule libraries against pathogenic bacteria is often challenged by a low hit rate due to limited uptake, underrepresentation of antibiotic structural motifs, and assays that do not resemble the infection conditions. To address these limitations, we present a screen of a focused library of alkyl guanidinium compounds, a structural motif associated with antibiotic activity and enhanced uptake, under host-mimicking infection conditions against a panel of disease-associated bacteria. Several hit molecules were identified with activities against Gram-positive and Gram-negative bacteria, highlighting the fidelity of the general concept. We selected one compound (L15) for in-depth mode of action studies that exhibited bactericidal activity against methicillin-resistant Staphylococcus aureusUSA300 with a minimum inhibitory concentration of 1.5 μM. Structure-activity relationship studies confirmed the necessity of the guanidinium motif for antibiotic activity. The mode of action was investigated using affinity-based protein profiling with an L15probe and identified the signal peptidase IB (SpsB) as the most promising hit. Validation by activity assays, binding site identification, docking, and molecular dynamics simulations demonstrated SpsB activation by L15, a recently described mechanism leading to the dysregulation of protein secretion and cell death. Overall, this study highlights the need for unconventional screening strategies to identify novel antibiotics.

Published
2024
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14. tRNA epitranscriptome determines pathogenicity of the opportunistic pathogen Pseudomonas aeruginosa.

Author

Krueger, Jonas, Preusse, Matthias, Gomez, Nicolas Oswaldo, Frommeyer, Yannick Noah, Doberenz, Sebastian, Lorenz, Anne, Kordes, Adrian, Grobe, Svenja, Müsken, Mathias, Depledge, Daniel P., Svensson, Sarah L., Weiss, Siegfried, Kaever, Volkhard, Pich, Andreas, Sharma, Cynthia M., Ignatova, Zoya, and Häussler, Susanne

Subjects
PSEUDOMONAS aeruginosa, TRANSFER RNA, GENE expression, PATHOGENIC microorganisms, URIDINE
Abstract

The success of bacterial pathogens depends on the coordinated expression of virulence determinants. Regulatory circuits that drive pathogenesis are complex, multilayered, and incompletely understood. Here, we reveal that alterations in tRNA modifications define pathogenic phenotypes in the opportunistic pathogen Pseudomonas aeruginosa. We demonstrate that the enzymatic activity of GidA leads to the introduction of a carboxymethylaminomethyl modification in selected tRNAs. Modifications at the wobble uridine base (cmnm5U34) of the anticodon drives translation of transcripts containing rare codons. Specifically, in P. aeruginosa the presence of GidA-dependent tRNA modifications modulates expression of genes encoding virulence regulators, leading to a cellular proteomic shift toward pathogenic and well-adapted physiological states. Our approach of profiling the consequences of chemical tRNA modifications is general in concept. It provides a paradigm of how environmentally driven tRNA modifications govern gene expression programs and regulate phenotypic outcomes responsible for bacterial adaption to challenging habitats prevailing in the host niche. [ABSTRACT FROM AUTHOR]

Published
2024
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20. Isolation and Quantification of Bacterial Membrane Vesicles for Quantitative Metabolic Studies Using Mammalian Cell Cultures

Author

Universidad de Sevilla. Departamento de Microbiología, Kretschmer, Marcel, Müller, Julia, Henke, Petra, Otto, Viktoria, Arce Rodríguez, Alejandro, Müsken, Mathias, Jahn, Dieter, Borrero de Acuña, José Manuel, Neumann-Schaal, Meina, Wegner, Andre, Universidad de Sevilla. Departamento de Microbiología, Kretschmer, Marcel, Müller, Julia, Henke, Petra, Otto, Viktoria, Arce Rodríguez, Alejandro, Müsken, Mathias, Jahn, Dieter, Borrero de Acuña, José Manuel, Neumann-Schaal, Meina, and Wegner, Andre

Abstract

Bacterial membrane vesicles (BMVs) are produced by most bacteria and participate in various cellular processes, such as intercellular communication, nutrient exchange, and pathogenesis. Notably, these vesicles can contain virulence factors, including toxic proteins, DNA, and RNA. Such factors can contribute to the harmful effects of bacterial pathogens on host cells and tissues. Although the general effects of BMVs on host cellular physiology are well known, the underlying molecular mechanisms are less understood. In this study, we introduce a vesicle quantification method, leveraging the membrane dye FM4-64. We utilize a linear regression model to analyze the fluorescence emitted by stained vesicle membranes to ensure consistent and reproducible vesicle–host interaction studies using cultured cells. This method is particularly valuable for identifying host cellular processes impacted by vesicles and their specific cargo. Moreover, it outcompetes unreliable protein concentration-based methods. We (1) show a linear correlation between the number of vesicles and the fluorescence signal emitted from the FM4-64 dye; (2) introduce the “vesicle load” as a new semi-quantitative unit, facilitating more reproducible vesicle-cell culture interaction experiments; (3) show that a stable vesicle load yields consistent host responses when studying vesicles from Pseudomonas aeruginosa mutants; (4) demonstrate that typical vesicle isolation contaminants, such as flagella, do not significantly skew the metabolic response of lung epithelial cells to P. aeruginosa vesicles; and (5) identify inositol monophosphatase 1 (SuhB) as a pivotal regulator in the vesicle-mediated pathogenesis of P. aeruginosa.

Published
2023

26. Streptococcus pneumoniae Affects Endothelial Cell Migration in Microfluidic Circulation

Author

Kopenhagen, Anna, Ramming, Isabell, Camp, Belinda, Hammerschmidt, Sven, Fulde, Marcus, Müsken, Mathias, Steinert, Michael, and Bergmann, Simone

Subjects
Microbiology (medical), endothelium, cell migration, microfluidic, Wound healing, wound healing, pneumolysin, 500 Naturwissenschaften und Mathematik::570 Biowissenschaften, Biologie::570 Biowissenschaften, Biologie, Microbiology, Article, ddc:57, Streptococcus pneumoniae, Microfluidic, Pneumolysin, ddc:571, Veröffentlichung der TU Braunschweig, Endothelium, Publikationsfonds der TU Braunschweig, ddc:5
Abstract

Bloodstream infections caused by Streptococcus pneumoniae induce strong inflammatory and procoagulant cellular responses and affect the endothelial barrier of the vascular system. Bacterial virulence determinants, such as the cytotoxic pore-forming pneumolysin, increase the endothelial barrier permeability by inducing cell apoptosis and cell damage. As life-threatening consequences, disseminated intravascular coagulation followed by consumption coagulopathy and low blood pressure is described. With the aim to decipher the role of pneumolysin in endothelial damage and leakage of the vascular barrier in more detail, we established a chamber-separation cell migration assay (CSMA) used to illustrate endothelial wound healing upon bacterial infections. We used chambered inlets for cell cultivation, which, after removal, provide a cell-free area of 500 μm in diameter as a defined gap in primary endothelial cell layers. During the process of wound healing, the size of the cell-free area is decreasing due to cell migration and proliferation, which we quantitatively determined by microscopic live cell monitoring. In addition, differential immunofluorescence staining combined with confocal microscopy was used to morphologically characterize the effect of bacterial attachment on cell migration and the velocity of gap closure. In all assays, the presence of wild-type pneumococci significantly inhibited endothelial gap closure. Remarkably, even in the presence of pneumolysin-deficient pneumococci, cell migration was significantly retarded. Moreover, the inhibitory effect of pneumococci on the proportion of cell proliferation versus cell migration within the process of endothelial gap closure was assessed by implementation of a fluorescence-conjugated nucleoside analogon. We further combined the endothelial CSMA with a microfluidic pump system, which for the first time enabled the microscopic visualization and monitoring of endothelial gap closure in the presence of circulating bacteria at defined vascular shear stress values for up to 48 h. In accordance with our CSMA results under static conditions, the gap remained cell free in the presence of circulating pneumococci in flow. Hence, our combined endothelial cultivation technique represents a complex in vitro system, which mimics the vascular physiology as close as possible by providing essential parameters of the blood flow to gain new insights into the effect of pneumococcal infection on endothelial barrier integrity in flow.

Published
2022

27. Legionella pneumophila PPIase Mip Interacts with the Bacterial Proteins SspB, Lpc2061, and FlaA and Promotes Flagellation

Author

Universidad de Sevilla. Departamento de Microbiología, Bundesministerium für Bildung und Forschung (BMBF), Karagöz, Mustafa Safa, Ünal, Can Murat, Mayer, Benjamin E., Müsken, Mathias, Borrero de Acuña, José Manuel, Steinert, Michael, Universidad de Sevilla. Departamento de Microbiología, Bundesministerium für Bildung und Forschung (BMBF), Karagöz, Mustafa Safa, Ünal, Can Murat, Mayer, Benjamin E., Müsken, Mathias, Borrero de Acuña, José Manuel, and Steinert, Michael

Abstract

The peptidyl-prolyl-cis/trans-isomerase (PPIase) macrophage infectivity potentiator (Mip) contributes to the pathogenicity and fitness of L. pneumophila, the causative agent of Legionnaires’ disease. Here, we identified the stringent starvation protein SspB, hypothetical protein Lpc2061, and flagellin FlaA as bacterial interaction partners of Mip. The macrolide FK506, which inhibits the PPIase activity of Mip, interfered with the binding of Lpc2061. Moreover, we demonstrated that the N-terminal dimerization region and amino acid Y185 in the C-terminal PPIase domain of Mip are required for the binding of Lpc2061 and FlaA. The modeling of the interaction partners and global docking with Mip suggested nonoverlapping binding interfaces, and a molecular dynamic simulation predicted an increased stability for the tripartite interaction of Lpc2061, Mip, and FlaA. On the functional level, we demonstrated that Mip promotes L. pneumophila flagellation, which is positively influenced by the binding of Lpc2061 and reduced by FK506. Also, L. pneumophila mutants expressing the Y185A or the monomeric Mip variant, which bind less Lpc2061, were nonmotile, were less flagellated, and yielded less FlaA when quantified. To our knowledge, this is the first report in which a PPIase and its bacterial interaction partners were demonstrated to influence flagellation.

Published
2022

28. Cigarette Smoke Extract Disturbs Mitochondria-Regulated Airway Epithelial Cell Responses to Pneumococci

Author

Aghapour, Mahyar, primary, Tulen, Christy B. M., additional, Abdi Sarabi, Mohsen, additional, Weinert, Sönke, additional, Müsken, Mathias, additional, Relja, Borna, additional, van Schooten, Frederik-Jan, additional, Jeron, Andreas, additional, Braun-Dullaeus, Rüdiger, additional, Remels, Alexander H., additional, and Bruder, Dunja, additional

Published
2022
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32. Pseudomonas aeruginosa post‐translational responses to elevated c‐di‐GMP levels

Author

Bense, Sarina, primary, Witte, Julius, additional, Preuße, Matthias, additional, Koska, Michal, additional, Pezoldt, Lorena, additional, Dröge, Astrid, additional, Hartmann, Oliver, additional, Müsken, Mathias, additional, Schulze, Julia, additional, Fiebig, Timm, additional, Bähre, Heike, additional, Felgner, Sebastian, additional, Pich, Andreas, additional, and Häussler, Susanne, additional

Published
2022
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36. Congenital deficiency reveals critical role of ISG15 in skin homeostasis

Author

Malik, Muhammad Nasir Hayat, primary, Waqas, Syed Fakhar-ul-Hassnain, additional, Zeitvogel, Jana, additional, Cheng, Jingyuan, additional, Geffers, Robert, additional, Gouda, Zeinab Abu-Elbaha, additional, Elsaman, Ahmed Mahrous, additional, Radwan, Ahmed R., additional, Schefzyk, Matthias, additional, Braubach, Peter, additional, Auber, Bernd, additional, Olmer, Ruth, additional, Müsken, Mathias, additional, Roesner, Lennart M., additional, Gerold, Gisa, additional, Schuchardt, Sven, additional, Merkert, Sylvia, additional, Martin, Ulrich, additional, Meissner, Felix, additional, Werfel, Thomas, additional, and Pessler, Frank, additional

Published
2022
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40. Comparative abundance of cutaneous bacteria in Central European amphibians.

Author

VENCES, MIGUEL, SCHULZ, VANESSA, HELDT, LORENZ, KAMPRAD, FELIX, RUTHSATZ, KATHARINA, PREISSLER, KATHLEEN, MÜSKEN, MATHIAS, and STEINFARTZ, SEBASTIAN

Abstract

The composition of cutaneous (skin-associated) bacterial communities of amphibians has been intensively studied in light of the potential of some of these commensal bacterial taxa to mitigate infection with the chytrid fungi Batrachochytrium dendrobatidis (Bd) and B. salamandrivorans (Bsal). However, surprisingly, the absolute densities in which these bacteria occur on the skin are only poorly known. We here combine quantification of bacterial 16SrDNA copies from skin swabs by quantitative PCR with counts from scanning electron microscopy (SEM) images to assess and compare bacterial abundances on the skin of various central European amphibians. We focus on the fire salamander (Salamandra salamandra) which is severely threatened by the spread of Bsal. Based on counts from SEM pictures of selected skin parts, local densities of ~43,000 bacteria per mm² were ascertained in frogs, although the data are insufficient to understand whether these values apply to the whole body surface. Bacterial densities are doubtless much lower in fire salamanders in which we observed almost no bacteria in SEM examination. From qPCR data, we find: (i) statistically relevant differences in bacterial abundances among species, with the lowest abundances in terrestrial salamanders and the highest abundances in toads; (ii) higher bacterial loads in captive compared to wild fire salamanders, and much higher loads in Bsal-infected captive specimens, in agreement with the hypothesis that Bsalinfection leads to blooming of opportunistic bacteria that may cause secondary infection; (iii) an only weak decrease of bacterial load after repeated swabbing, in agreement with the hypothesis that skin swabs capture only a part of the bacteria of the swabbed skin surface. We discuss the multiple sources of uncertainty in absolute estimates of abundances of cutaneous bacteria and suggest further research to clarify and reduce these uncertainties. [ABSTRACT FROM AUTHOR]

Published
2022

43. Loss of Hem1 disrupts macrophage function and impacts migration, phagocytosis, and integrin-mediated adhesion

Author

Stahnke, Stephanie, primary, Döring, Hermann, additional, Kusch, Charly, additional, de Gorter, David J.J., additional, Dütting, Sebastian, additional, Guledani, Aleks, additional, Pleines, Irina, additional, Schnoor, Michael, additional, Sixt, Michael, additional, Geffers, Robert, additional, Rohde, Manfred, additional, Müsken, Mathias, additional, Kage, Frieda, additional, Steffen, Anika, additional, Faix, Jan, additional, Nieswandt, Bernhard, additional, Rottner, Klemens, additional, and Stradal, Theresia E.B., additional

Published
2021
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44. Parallel evolutionary paths to produce more than one biofilm phenotype

Author

Thöming, Janne G, Tomasch, Jürgen, Preusse, Matthias, Koska, Michal, Grahl, Nora, Pohl, Sarah, Willger, Sven D, Kaever, Volkhard, Müsken, Mathias, Häussler, Susanne, and HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany.

Subjects
Biofilms, Next-generation sequencing, biochemical phenomena, metabolism, and nutrition
Abstract

Studying parallel evolution of similar traits in independent within-species lineages provides an opportunity to address evolutionary predictability of molecular changes underlying adaptation. In this study, we monitored biofilm forming capabilities, motility, and virulence phenotypes of a plethora of phylogenetically diverse clinical isolates of the opportunistic pathogen Pseudomonas aeruginosa. We also recorded biofilm-specific and planktonic transcriptional responses. We found that P. aeruginosa isolates could be stratified based on the production of distinct organismal traits. Three major biofilm phenotypes, which shared motility and virulence phenotypes, were produced repeatedly in several isolates, indicating that the phenotypes evolved via parallel or convergent evolution. Of note, while we found a restricted general response to the biofilm environment, the individual groups of biofilm phenotypes reproduced biofilm transcriptional profiles that included the expression of well-known biofilm features, such as surface adhesive structures and extracellular matrix components. Our results provide insights into distinct ways to make a biofilm and indicate that genetic adaptations can modulate multiple pathways for biofilm development that are followed by several independent clinical isolates. Uncovering core regulatory pathways that drive biofilm-associated growth and tolerance towards environmental stressors promises to give clues to host and environmental interactions and could provide useful targets for new clinical interventions.

Published
2020

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