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Abstract
Chromogranin A (CgA) is the precursor of several antimicrobial peptides, such as Catestatin (Cts, bovine CgA344-364), initially described as a potent inhibitor of catecholamines. This peptide displays direct antimicrobial activities and contributes to immune system regulation. The aim of the present study is to investigate a designed peptide based on Cts to fight infections against superbugs and more particularly Staphylococcus aureus. In addition to Cateslytin (Ctl, bovine CgA344-358), the active domain of Catestatin, several peptides including dimers, D-isomer and the new designed peptide DOPA-K-DOPA-K-DOPA-TLRGGE-RSMRLSFRARGYGFR (Dopa5T-Ctl) were prepared and tested. Cateslytin is resistant to bacterial degradation and does not induce bacterial resistance. The interaction of Catestatin with immune dermal cells (dendritic cells DC1a, dermal macrophages CD14 and macrophages) was analyzed by using confocal microscopy and cytokine release assay. The dimers and D-isomer of Ctl were tested against a large variety of bacteria showing the potent antibacterial activity of the D-isomer. The peptide Dopa5T-Ctl is able to induce the self-killing of S. aureus after release of Ctl by the endoprotease Glu-C produced by this pathogen. It permits localized on-demand delivery of the antimicrobial drug directly at the infectious site.
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1 Institut National de la Santé et de la Recherche Médicale UMR_S 1121, Federation of Translational Medicine Faculty, of Odontology, University of Strasbourg, Hôpital Civil, Porte de L’Hôpital, BioMaterials and BioEngeneering, Strasbourg, France (GRID:grid.11843.3f) (ISNI:0000 0001 2157 9291); University of Calabria, Department of Biology, Ecology and Earth Science, Arcavacata di Rende, Italy (GRID:grid.7778.f) (ISNI:0000 0004 1937 0319)
2 Institut National de la Santé et de la Recherche Médicale UMR_S 1121, Federation of Translational Medicine Faculty, of Odontology, University of Strasbourg, Hôpital Civil, Porte de L’Hôpital, BioMaterials and BioEngeneering, Strasbourg, France (GRID:grid.11843.3f) (ISNI:0000 0001 2157 9291)
3 Institut National de la Santé et de la Recherche Médicale UMR_S 1121, Federation of Translational Medicine Faculty, of Odontology, University of Strasbourg, Hôpital Civil, Porte de L’Hôpital, BioMaterials and BioEngeneering, Strasbourg, France (GRID:grid.11843.3f) (ISNI:0000 0001 2157 9291); University of Strasbourg, Faculty of Medicine, Strasbourg, France (GRID:grid.11843.3f) (ISNI:0000 0001 2157 9291)
4 Institut National de la Santé et de la Recherche Médicale UMR_S 1121, Federation of Translational Medicine Faculty, of Odontology, University of Strasbourg, Hôpital Civil, Porte de L’Hôpital, BioMaterials and BioEngeneering, Strasbourg, France (GRID:grid.11843.3f) (ISNI:0000 0001 2157 9291); University of Strasbourg, Faculty of Medicine, Strasbourg, France (GRID:grid.11843.3f) (ISNI:0000 0001 2157 9291); University of Strasbourg, Médecine Intensive-Réanimation, Hautepierre Hospital, Hôpitaux Universitaires, Strasbourg, Federation of Translational Medicine, Faculty of Medicine, Strasbourg, France (GRID:grid.11843.3f) (ISNI:0000 0001 2157 9291)
5 University of Strasbourg, Centre National de la Recherche Scientifique, Institut des Neurosciences Cellulaires et Intégratives, Strasbourg, France (GRID:grid.11843.3f) (ISNI:0000 0001 2157 9291)
6 Pluridisciplinary Institute Hubert Curien, UMR 7178, University of Strasbourg, Centre National de la Recherche Scientifique, Laboratory of Bio-Organic Mass Spectrometry, Analytical Sciences Department, Strasbourg, France (GRID:grid.11843.3f) (ISNI:0000 0001 2157 9291)
7 Institut National de la Santé et de la Recherche Médicale UMR_S 1121, Federation of Translational Medicine Faculty, of Odontology, University of Strasbourg, Hôpital Civil, Porte de L’Hôpital, BioMaterials and BioEngeneering, Strasbourg, France (GRID:grid.11843.3f) (ISNI:0000 0001 2157 9291); University of Strasbourg, Faculty of Odontology, Strasbourg, France (GRID:grid.11843.3f) (ISNI:0000 0001 2157 9291)