Catestatin in innate immunity and Cateslytin-derived peptides

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 particularlyStaphylococcus 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.

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Fig: Outline of the study. 1—Immunomodulation: Interactions of Cts and its derived-peptides with immune cells are investigated; 2—The antibacterial activities of Ctl and the derived- peptides are examined; 3—The tri-blocks peptide Dopa5T-Ctl for the on-demand delivery of Ctl is tested.

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.

Scavello, F., Mutschler, A., Hellé, S. et al. Catestatin in innate immunity and Cateslytin-derived peptides against superbugs. Sci Rep 11, 15615 (2021). https://doi.org/10.1038/s41598-021-94749-6

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