title: Intestinal mucus affinity and biological activity of an orally administered antibacterial and anti-inflammatory peptide.
abstract: 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.
  
  
  METHODS
  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.
authors.affiliation: Institute of Medical Microbiology and Hospital Epidemiology, Hannover Medical School, Hannover, Germany.
authors.forename: Aline
authors.initials: A
authors.lastname: Dupont
authors.affiliation: Division of Biophysics, Research Center Borstel, Borstel, Germany.
authors.forename: Yani
authors.initials: Y
authors.lastname: Kaconis
authors.affiliation: Institute of Medical Microbiology and Hospital Epidemiology, Hannover Medical School, Hannover, Germany.
authors.forename: Ines
authors.identifier: http://orcid.org/0000-0002-3812-2690
authors.initials: I
authors.lastname: Yang
authors.affiliation: Institute of Medical Microbiology and Hospital Epidemiology, Hannover Medical School, Hannover, Germany.
authors.forename: Thorben
authors.initials: T
authors.lastname: Albers
authors.affiliation: Institute of Medical Microbiology and Hospital Epidemiology, Hannover Medical School, Hannover, Germany.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Woltemate
authors.affiliation: Division of Biophysics, Research Center Borstel, Borstel, Germany.
authors.forename: Lena
authors.initials: L
authors.lastname: Heinbockel
authors.affiliation: Microbiology and Tumor Biology Center, Karolinska Institute, Stockholm, Sweden.
authors.forename: Mats
authors.initials: M
authors.lastname: Andersson
authors.affiliation: Institute of Medical Microbiology and Hospital Epidemiology, Hannover Medical School, Hannover, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Suerbaum
authors.affiliation: Division of Biophysics, Research Center Borstel, Borstel, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Brandenburg
authors.affiliation: Institute of Medical Microbiology and Hospital Epidemiology, Hannover Medical School, Hannover, Germany.
authors.forename: Mathias W
authors.initials: MW
authors.lastname: Hornef
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002478:Cells, Cultured; D023082:Defensins; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005260:Female; D054884:Host-Pathogen Interactions / Q000502:physiology; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000382:microbiology; D008810:Mice, Inbred C57BL; D064307:Microbiota / Q000187:drug effects; D009093:Mucus / Q000378:metabolism / Q000382:microbiology; D010446:Peptide Fragments / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D011506:Proteins / Q000378:metabolism; D012480:Salmonella Infections / Q000188:drug therapy / Q000378:metabolism / Q000382:microbiology; D012486:Salmonella typhimurium / Q000187:drug effects / Q000378:metabolism / Q000502:physiology
chemical_list: D000900:Anti-Bacterial Agents; D000893:Anti-Inflammatory Agents; D023082:Defensins; D010446:Peptide Fragments; D011506:Proteins; C107641:cryptdin 2
keywords: ANTI-BACTERIAL MUCOSAL IMMUNITY; BACTERIAL INFECTION; MUCOSAL BARRIER; MUCOSAL INFECTION