Evaluation of colostrum-derived human mammary-associated serum amyloid A3 (M-SAA3) protein and peptide derivatives for the prevention of enteric infection: In vitro and in murine models of intestinal disease

Gillian E. Gardiner, Sarah O'Flaherty, Pat G. Casey, Annika Weber, Thomas L. McDonald, Michael Cronin, Colin Hill, Reynolds P. Ross, Cormac G.M. Gahan, Fergus Shanahan

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

In vitro experiments confirmed that a 10-mer peptide derived from human mammary-associated serum amyloid A3 (M-SAA3) protected intestinal epithelial cells from enteropathogenic Escherichia coli (EPEC) adherence. The entire 42-mer human M-SAA3 protein was even more effective, reducing EPEC binding by 72% relative to untreated cells (P<0.05), compared with 25% and 57% reductions for the human 10-mer and Lactobacillus GG, respectively. However, none of the M-SAA3 peptides reduced Salmonella invasion in vitro (P>0.05). Each of the M-SAA3 10-mer peptides and the 42-mer was then administered orally to mice at 500 μg day-1 for 4 days before deliberate infection with either Citrobacter rodentium (mouse model of EPEC) or Salmonella Typhimurium. None of the peptides protected against Salmonella infection and the 42-mer may even increase infection, as there was a trend towards increased Salmonella counts in the liver and small intestine in 42-mer-treated mice compared with those in sodium acetate-treated control mice. Citrobacter counts were reduced in the caecum of mice administered the 42-mer relative to a scrambled 10-mer (P<0.05), but not compared with the sodium acetate control and no reductions were observed in the faeces or colon. Overall, although promising anti-infective activity was demonstrated in vitro, neither the 42-mer M-SAA3 protein nor a 10-mer peptide derivative prevented enteric infection in the animal models tested.

Original languageEnglish (US)
Pages (from-to)404-413
Number of pages10
JournalFEMS Immunology and Medical Microbiology
Volume55
Issue number3
DOIs
StatePublished - Apr 2009

Keywords

  • Enteropathogenic Escherichia coli
  • Infection
  • Mammary associated serum amyloid A3
  • Mouse
  • Salmonella

ASJC Scopus subject areas

  • Immunology and Allergy
  • Microbiology
  • Immunology
  • Microbiology (medical)
  • Infectious Diseases

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