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.
Keywords: Innate immunity, antimicrobial peptides, antibiotics, chromogranins, catestatin, chromofungin, Staphylococcus aureus, Salmonella enteritis, neutrophils, bacterial proteases, synergy, neuroendocrine system, immune system.
Current Medicinal Chemistry
Title:Chromogranin A-Derived Peptides Are Involved in Innate Immunity
Volume: 19 Issue: 24
Author(s): R. Aslam, M. Atindehou, T. Lavaux, Y. Haïkel, F. Schneider and M. -H. Metz-Boutigue
Affiliation:
Keywords: Innate immunity, antimicrobial peptides, antibiotics, chromogranins, catestatin, chromofungin, Staphylococcus aureus, Salmonella enteritis, neutrophils, bacterial proteases, synergy, neuroendocrine system, immune system.
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.
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Aslam R., Atindehou M., Lavaux T., Haïkel Y., Schneider F. and -H. Metz-Boutigue M., Chromogranin A-Derived Peptides Are Involved in Innate Immunity, Current Medicinal Chemistry 2012; 19 (24) . https://dx.doi.org/10.2174/092986712802430063
DOI https://dx.doi.org/10.2174/092986712802430063 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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