Format

Send to

Choose Destination
Gut. 2015 Feb;64(2):222-32. doi: 10.1136/gutjnl-2014-307150. Epub 2014 May 7.

Intestinal mucus affinity and biological activity of an orally administered antibacterial and anti-inflammatory peptide.

Author information

1
Institute of Medical Microbiology and Hospital Epidemiology, Hannover Medical School, Hannover, Germany.
2
Division of Biophysics, Research Center Borstel, Borstel, Germany.
3
Microbiology and Tumor Biology Center, Karolinska Institute, Stockholm, Sweden.

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.

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.

KEYWORDS:

ANTI-BACTERIAL MUCOSAL IMMUNITY; BACTERIAL INFECTION; MUCOSAL BARRIER; MUCOSAL INFECTION

PMID:
24811998
DOI:
10.1136/gutjnl-2014-307150
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center