Chromogranin A-derived peptides are involved in innate immunity.

Abstract

New endogenous antimicrobial peptides (AMPs) derived from chromogranin A (CgA) are secreted by nervous, endocrine and immune cells during stress. They display antimicrobial activities by lytic effects at micromolar range using a pore-forming mechanism against Gram-positive bacteria, filamentous fungi and yeasts. These AMPs can also penetrate quickly into neutrophils (without lytic effects), where, similarly to "cell penetrating peptides", they interact with cytoplasmic calmodulin, and induce calcium influx via Store Operated Channels therefore triggering neutrophils activation. Staphylococcus aureus and Salmonella enteritis are bacteria responsible for severe infections. We investigated here the effects of S. aureus and S. enteritis bacterial proteases on CgA-derived peptides and evaluated their antimicrobial activities. We showed that the Glu-C protease produced by S. aureus V8 induces the loss of the AMPs antibacterial activities and produces new antifungal peptides. In addition, four antimicrobial CGA-derived peptides (chromofungin, procatestatin, human/bovine catestatin) are degraded when treated with bacterial supernatants from S. aureus and S. enteritis, whereas, cateslytin, the short active form of catestatin, resists to this degradation. Finally, we demonstrate that several antimicrobial CgA-derived peptides are able to act synergistically with antibiotics against bacteria and fungi indicating their roles in innate defense.

• Authors: R Aslam, M Atindehou, T Lavaux, Y Haïkel, F Schneider, M-H Metz-Boutigue
• Journal: Current medicinal chemistry (Curr Med Chem) Vol. 19 Issue 24 Pg. 4115-23 ( 2012) ISSN: 1875-533X [Electronic] United Arab Emirates
• PMID: 22834801 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antimicrobial Cationic Peptides
• Chromogranin A
• Peptide Fragments
• chromofungin
• chromogranin A (344-364)
• vasostatin I
• Serine Endopeptidases
• glutamyl endopeptidase

Topics

• Amino Acid Sequence
• Animals
• Antimicrobial Cationic Peptides (chemistry, immunology, pharmacology)
• Cattle
• Chromogranin A (chemistry, immunology, metabolism, pharmacology)
• Fungi (drug effects)
• Host-Pathogen Interactions (immunology)
• Humans
• Immunity, Innate
• Molecular Sequence Data
• Neutrophils (immunology, metabolism)
• Peptide Fragments (chemistry, immunology, pharmacology)
• Salmonella (drug effects)
• Serine Endopeptidases (metabolism)
• Staphylococcus aureus (drug effects)