OBJECTIVE: Antimicrobial peptides (AMP) provide protection from infection by pathogenic microorganisms and restrict bacterial growth at epithelial surfaces to maintain mucosal homeostasis. In addition, they exert a significant anti-inflammatory activity. Here we analysed the anatomical distribution and biological activity of an orally administered AMP in the context of bacterial infection and host-microbial homeostasis. DESIGN: The anatomical distribution as well as antibacterial and anti-inflammatory activity of the endogenous AMP cryptdin 2 and the synthetic peptide Pep19-2.5 at the enteric mucosal surface were analysed by immunostaining, functional viability and stimulation assays, an oral Salmonella enterica subsp. enterica sv. Typhimurium (S. Typhimurium) model and comparative microbiota analysis. RESULTS: Endogenous cryptdin 2 was found attached to bacteria of the enteric microbiota within the intestinal mucus layer. Similarly, the synthetic peptide Pep19-2.5 attached rapidly to bacterial cells, exhibited a marked affinity for the intestinal mucus layer in vivo, altered the structural organisation of endotoxin in a mucus matrix and demonstrated potent anti-inflammatory and antibacterial activity. Oral Pep19-2.5 administration induced significant changes in the composition of the enteric microbiota as determined by high-throughput 16S rDNA sequencing. This may have contributed to the only transient improvement of the clinical symptoms after oral infection with S. Typhimurium. CONCLUSIONS: Our findings demonstrate the anti-inflammatory activity and mucus affinity of the synthetic AMP Pep19-2.5 and characterise the influence on microbiota composition and enteropathogen infection after oral administration. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
OBJECTIVE: Antimicrobial peptides (AMP) provide protection from infection by pathogenic microorganisms and restrict bacterial growth at epithelial surfaces to maintain mucosal homeostasis. In addition, they exert a significant anti-inflammatory activity. Here we analysed the anatomical distribution and biological activity of an orally administered AMP in the context of bacterial infection and host-microbial homeostasis. DESIGN: The anatomical distribution as well as antibacterial and anti-inflammatory activity of the endogenous AMP cryptdin 2 and the synthetic peptide Pep19-2.5 at the enteric mucosal surface were analysed by immunostaining, functional viability and stimulation assays, an oral Salmonella enterica subsp. enterica sv. Typhimurium (S. Typhimurium) model and comparative microbiota analysis. RESULTS: Endogenous cryptdin 2 was found attached to bacteria of the enteric microbiota within the intestinal mucus layer. Similarly, the synthetic peptide Pep19-2.5 attached rapidly to bacterial cells, exhibited a marked affinity for the intestinal mucus layer in vivo, altered the structural organisation of endotoxin in a mucus matrix and demonstrated potent anti-inflammatory and antibacterial activity. Oral Pep19-2.5 administration induced significant changes in the composition of the enteric microbiota as determined by high-throughput 16S rDNA sequencing. This may have contributed to the only transient improvement of the clinical symptoms after oral infection with S. Typhimurium. CONCLUSIONS: Our findings demonstrate the anti-inflammatory activity and mucus affinity of the synthetic AMP Pep19-2.5 and characterise the influence on microbiota composition and enteropathogen infection after oral administration. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
Authors: Maarten Coorens; Viktoria A F Schneider; A Marit de Groot; Albert van Dijk; Marjolein Meijerink; Jerry M Wells; Maaike R Scheenstra; Edwin J A Veldhuizen; Henk P Haagsman Journal: J Immunol Date: 2017-07-14 Impact factor: 5.422
Authors: Kenneth Peuker; Stefanie Muff; Jun Wang; Sven Künzel; Esther Bosse; Yvonne Zeissig; Giuseppina Luzzi; Marijana Basic; Anne Strigli; Andrea Ulbricht; Arthur Kaser; Alexander Arlt; Triantafyllos Chavakis; Gijs R van den Brink; Clemens Schafmayer; Jan-Hendrik Egberts; Thomas Becker; Marco E Bianchi; André Bleich; Christoph Röcken; Jochen Hampe; Stefan Schreiber; John F Baines; Richard S Blumberg; Sebastian Zeissig Journal: Nat Med Date: 2016-04-04 Impact factor: 53.440
Authors: Kaiyi Zhang; Aline Dupont; Natalia Torow; Frederik Gohde; Fredrik Gohde; Sara Leschner; Stefan Lienenklaus; Siegfried Weiss; Melanie M Brinkmann; Mark Kühnel; Michael Hensel; Marcus Fulde; Mathias W Hornef Journal: PLoS Pathog Date: 2014-09-11 Impact factor: 6.823