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End date: 2024 × End date: 2024 × Start date: 2020 × DDC: 540 × DDC: 570 × DDC: 610 ×

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    Targeting extracellular lectins of Pseudomonas aeruginosa with glycomimetic liposomes
    (London [u.a.] : RSC, 2021) Metelkina, Olga; Huck, Benedikt; O'Connor, Jonathan S.; Koch, Marcus; Manz, Andreas; Lehr, Claus-Michael; Titz, Alexander
    The antimicrobial resistance crisis requires novel approaches for the therapy of infections especially with Gram-negative pathogens. Pseudomonas aeruginosa is defined as priority 1 pathogen by the WHO and thus of particular interest. Its drug resistance is primarily associated with biofilm formation and essential constituents of its extracellular biofilm matrix are the two lectins, LecA and LecB. Here, we report microbial lectin-specific targeted nanovehicles based on liposomes. LecA- and LecB-targeted phospholipids were synthesized and used for the preparation of liposomes. These liposomes with varying surface ligand density were then analyzed for their competitive and direct lectin binding activity. We have further developed a microfluidic device that allowed the optical detection of the targeting process to the bacterial lectins. Our data showed that the targeted liposomes are specifically binding to their respective lectin and remain firmly attached to surfaces containing these lectins. This synthetic and biophysical study provides the basis for future application in targeted antibiotic delivery to overcome antimicrobial resistance.
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    The more the merrier: effects of macromolecular crowding on the structure and dynamics of biological membranes
    (Oxford [u.a.] : Wiley-Blackwell, 2020) Löwe, Maryna; Kalacheva, Milara; Boersma, Arnold J.; Kedrov, Alexej
    Proteins are essential and abundant components of cellular membranes. Being densely packed within the limited surface area, proteins fulfil essential tasks for life, which include transport, signalling and maintenance of cellular homeostasis. The high protein density promotes nonspecific interactions, which affect the dynamics of the membrane-associated processes, but also contribute to higher levels of membrane organization. Here, we provide a comprehensive summary of the most recent findings of diverse effects resulting from high protein densities in both living membranes and reconstituted systems and display why the crowding phenomenon should be considered and assessed when studying cellular pathways. Biochemical, biophysical and computational studies reveal effects of crowding on the translational mobility of proteins and lipids, oligomerization and clustering of integral membrane proteins, and also folding and aggregation of proteins at the lipid membrane interface. The effects of crowding pervade to larger length scales, where interfacial and transmembrane crowding shapes the lipid membrane. Finally, we discuss the design and development of fluorescence-based sensors for macromolecular crowding and the perspectives to use those in application to cellular membranes and suggest some emerging topics in studying crowding at biological interfaces. © 2020 The Authors. The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies
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    ConsensusPrime—A Bioinformatic Pipeline for Ideal Consensus Primer Design
    (Basel : MDPI, 2022) Collatz, Maximilian; Braun, Sascha D.; Monecke, Stefan; Ehricht, Ralf
    Background: High-quality oligonucleotides for molecular amplification and detection procedures of diverse target sequences depend on sequence homology. Processing input sequences and identifying homogeneous regions in alignments can be carried out by hand only if they are small and contain sequences of high similarity. Finding the best regions for large and inhomogeneous alignments needs to be automated. Results: The ConsensusPrime pipeline was developed to sort out redundant and technical interfering data in multiple sequence alignments and detect the most homologous regions from multiple sequences. It automates the prediction of optimal consensus primers for molecular analytical and sequence-based procedures/assays. Conclusion: ConsensusPrime is a fast and easy-to-use pipeline for predicting optimal consensus primers that is executable on local systems without depending on external resources and web services. An implementation in a Docker image ensures platform-independent executability and installability despite the combination of multiple programs. The source code and installation instructions are publicly available on GitHub.