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| Verfasst von: | Werner, Julia [VerfasserIn]  |
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| | Umstätter, Florian [VerfasserIn] |
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| | Böhmann, Manuel Ben [VerfasserIn] |
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| | Müller, Hannah [VerfasserIn] |
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| | Beijer, Barbro [VerfasserIn] |
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| | Hertlein, Tobias [VerfasserIn] |
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| | Kaschnitz, Laura [VerfasserIn] |
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| | Bram, Veronika [VerfasserIn] |
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| | Kleist, Christian [VerfasserIn] |
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| | Klika, Karel D. [VerfasserIn] |
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| | Mühlberg, Eric [VerfasserIn] |
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| | Braune, Gabriel [VerfasserIn] |
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| | Wohlfart, Sabrina [VerfasserIn] |
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| | Gärtner, Martin [VerfasserIn] |
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| | Peter, Silke [VerfasserIn] |
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| | Zimmermann, Stefan [VerfasserIn] |
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| | Haberkorn, Uwe [VerfasserIn] |
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| | Ohlsen, Knut [VerfasserIn] |
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| | Brötz-Oesterhelt, Heike [VerfasserIn] |
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| | Mier, Walter [VerfasserIn] |
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| | Uhl, Philipp [VerfasserIn] |
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| Titel: | Conjugation of polycationic peptides extends the efficacy spectrum of β-lactam antibiotics |
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| Verf.angabe: | Julia Werner, Florian Umstätter, Manuel B. Böhmann, Hannah Müller, Barbro Beijer, Tobias Hertlein, Laura Kaschnitz, Veronika Bram, Christian Kleist, Karel D. Klika, Eric Mühlberg, Gabriel Braune, Sabrina Wohlfart, Martin Gärtner, Silke Peter, Stefan Zimmermann, Uwe Haberkorn, Knut Ohlsen, Heike Brötz-Oesterhelt, Walter Mier, and Philipp Uhl |
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| E-Jahr: | 2024 |
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| Jahr: | December 26, 2024 |
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| Umfang: | 12 S. |
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| Illustrationen: | Illustrationen |
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| Fussnoten: | Online verfügbar: 05. November 2024 ; Gesehen am 20.05.2025 |
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| Titel Quelle: | Enthalten in: Advanced science |
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| Ort Quelle: | Weinheim : Wiley-VCH, 2014 |
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| Jahr Quelle: | 2024 |
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| Band/Heft Quelle: | 11(2024), 48, Artikel-ID 2411406, Seite 1-12 |
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| ISSN Quelle: | 2198-3844 |
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| Abstract: | Antibiotic-resistant enterococci represent a significant global health challenge. Unfortunately, most β-lactam antibiotics are not applicable for enterococcal infections due to intrinsic resistance. To extend their antimicrobial spectrum, polycationic peptides are conjugated to examples from each of the four classes of β-lactam antibiotics. Remarkably, the β-lactam-peptide conjugates gained an up to 1000-fold increase in antimicrobial activity against vancomycin-susceptible and vancomycin-resistant enterococci. Even against β-lactam-resistant Gram-negative strains, the conjugates are found to be effective despite their size exceeding the exclusion volume of porins. The extraordinary gain of activity can be explained by an altered mode of killing. Of note, the conjugates showed a concentration-dependent activity in contrast to the parent β-lactam antibiotics that exhibited a time-dependent mode of action. In comparison to the parent β-lactams, the conjugates showed altered affinities to the penicillin-binding proteins. Furthermore, it is found that peptide conjugation also resulted in a different elimination route of the compounds when administered to rodents. In mice systemically infected with vancomycin-resistant enterococci, treatment with a β-lactam-peptide conjugate reduced bacterial burden in the liver compared to its originator. Therefore, peptide modification of β-lactam antibiotics represents a promising platform strategy to broaden their efficacy spectrum, particularly against enterococci. |
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| DOI: | doi:10.1002/advs.202411406 |
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| URL: | Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.
kostenfrei: Volltext: https://doi.org/10.1002/advs.202411406 |
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| | kostenfrei: Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1002/advs.202411406 |
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| | DOI: https://doi.org/10.1002/advs.202411406 |
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| Datenträger: | Online-Ressource |
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| Sprache: | eng |
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| Sach-SW: | enterococci |
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| | polycationic peptides |
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| | resistance |
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| | β-lactam antibiotics |
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| K10plus-PPN: | 192613432X |
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| Verknüpfungen: | → Zeitschrift |
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Conjugation of polycationic peptides extends the efficacy spectrum of β-lactam antibiotics / Werner, Julia [VerfasserIn]; December 26, 2024 (Online-Ressource)
