Antibacterial activity of a dual peptide targeting the Escherichia coli sliding clamp and the ribosome†
| Autor: | Dominique Burnouf, Florian Veillard, Anne-Marie Lobstein, Clément Monsarrat, Jean-Marc Reichhart, Camille Noûs, Guillaume Compain, Philippe Wolff, Gilles Guichard, Christophe André, Jérôme Wagner |
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| Přispěvatelé: | Chimie et Biologie des Membranes et des Nanoobjets (CBMN), École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Modèles Insectes de l'Immunité Innée (M3I), Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Architecture et Réactivité de l'ARN (ARN), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Cogitamus, Biotechnologie et signalisation cellulaire (BSC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut de recherche de l'Ecole de biotechnologie de Strasbourg (IREBS), Université de Bordeaux (UB)-École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université de Strasbourg (UNISTRA)-Institut de recherche de l'Ecole de biotechnologie de Strasbourg (IREBS)-Centre National de la Recherche Scientifique (CNRS), Wagner, Jerome |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
[SDV.BIO]Life Sciences [q-bio]/Biotechnology
DNA polymerase Peptide medicine.disease_cause Biochemistry Genetics and Molecular Biology (miscellaneous) Biochemistry Ribosome 03 medical and health sciences medicine Molecular Biology Escherichia coli 030304 developmental biology chemistry.chemical_classification 0303 health sciences DNA clamp biology 030306 microbiology Sciences du Vivant [q-bio]/Biotechnologies Processivity biology.organism_classification [SDV.BIO] Life Sciences [q-bio]/Biotechnology 3. Good health Chemistry chemistry Chemistry (miscellaneous) biology.protein Antibacterial activity Bacteria |
| Zdroj: | RSC Chemical Biology RSC Chemical Biology, Royal Society of Chemistry, 2020, ⟨10.1039/D0CB00060D⟩ RSC Chemical Biology, 2020, ⟨10.1039/D0CB00060D⟩ |
| ISSN: | 2633-0679 |
| DOI: | 10.1039/D0CB00060D⟩ |
| Popis: | The bacterial processivity factor, or sliding clamp (SC), is a target of choice for new antibacterial drugs development. We have previously developed peptides that target Escherichia coli SC and block its interaction with DNA polymerases in vitro. Here, one such SC binding peptide was fused to a Proline-rich AntiMicrobial Peptide (PrAMP) to allow its internalization into E. coli cells. Co-immunoprecipitation assays with a N-terminally modified bifunctional peptide that still enters the bacteria but fails to interact with the bacterial ribosome, the major target of PrAMPs, demonstrate that it actually interacts with the bacterial SC. Moreover, when compared to SC non-binding controls, this peptide induces a ten-fold higher antibacterial activity against E. coli, showing that the observed antimicrobial activity is linked to SC binding. Finally, an unmodified bifunctional compound significantly increases the survival of Drosophila melanogaster flies challenged by an E. coli infection. Our study demonstrates the potential of PrAMPs to transport antibiotics into the bacterial cytoplasm and validates the development of drugs targeting the bacterial processivity factor of Gram-negative bacteria as a promising new class of antibiotics. Bifunctional peptides targeting both the translation and the replication machineries have been developed and shown to act as new antimicrobials. |
| Databáze: | OpenAIRE |
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