Authors: Aslam, R.; Atindehou, M.; Lavaux, T.; Haikel, Y.; Schneider, F.; -H. Metz-Boutigue, M.

Source: Current Medicinal Chemistry, Volume 19, Number 24, August 2012 , pp. 4115-4123(9)

Publisher: Bentham Science Publishers

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

Document Type: Research article

DOI: http://dx.doi.org/10.2174/092986712802430063

Publication date: 2012-08-01

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• Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.

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