Catestatin in innate immunity and Cateslytin-derived peptides against superbugs

• Published in: Scientific reports 2021-08, Vol.11 (1), p.15615-14, Article 15615
• Main Authors: Scavello, Francesco, Mutschler, Angela, Hellé, Sophie, Schneider, Francis, Chasserot-Golaz, Sylvette, Strub, Jean-Marc, Cianferani, Sarah, Haikel, Youssef, Metz-Boutigue, Marie-Hélène
• Format: Article
• Language: English
• Subjects: 631/326; 631/45; 692/163; 692/699; Animals; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Antibacterial activity; Antimicrobial agents; Antimicrobial peptides; Antimicrobial Peptides - chemistry; Antimicrobial Peptides - pharmacology; Biodegradation; Catecholamines; Cattle; CD14 antigen; Chemical Sciences; Chromogranin A - chemistry; Chromogranin A - pharmacology; Confocal microscopy; Cytokines; Cytotoxicity; Dendritic cells; Dendritic Cells - drug effects; Dendritic Cells - immunology; Dihydroxyphenylalanine; Humanities and Social Sciences; Humans; Immune system; Immunity, Innate - drug effects; Innate immunity; Life Sciences; Lymphocytes T; Macrophages; Macrophages - drug effects; Macrophages - immunology; Macrophages - metabolism; Microbial Sensitivity Tests; multidisciplinary; Peptide Fragments - pharmacology; Peptides; Science; Science (multidisciplinary); Staphylococcus aureus; Staphylococcus aureus - drug effects; Staphylococcus aureus - immunology
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-021-94749-6

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 (Dopa 5 T-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 Dopa 5 T-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.