title: 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.
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 mug 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.
authors.affiliation: Teagasc, Moorepark Food Research Center, Fermoy Co, Cork, Ireland. ggardiner@wit.ie
authors.forename: Gillian E
authors.initials: GE
authors.lastname: Gardiner
authors.forename: Sarah
authors.initials: S
authors.lastname: O'Flaherty
authors.forename: Pat G
authors.initials: PG
authors.lastname: Casey
authors.forename: Annika
authors.initials: A
authors.lastname: Weber
authors.forename: Thomas L
authors.initials: TL
authors.lastname: McDonald
authors.forename: Michael
authors.initials: M
authors.lastname: Cronin
authors.forename: Colin
authors.initials: C
authors.lastname: Hill
authors.forename: Reynolds P
authors.initials: RP
authors.lastname: Ross
authors.forename: Cormac G M
authors.initials: CG
authors.lastname: Gahan
authors.forename: Fergus
authors.initials: F
authors.lastname: Shanahan
mesh_terms: D000818:Animals; D001422:Bacterial Adhesion / Q000187:drug effects*; D002432:Cecum / Q000382:microbiology; D002460:Cell Line; D044082:Citrobacter rodentium / Q000187:drug effects; D003106:Colon / Q000382:microbiology; D004751:Enteritis / Q000517:prevention & control*; D004756:Enterobacteriaceae Infections / Q000517:prevention & control*; D004926:Escherichia coli / Q000187:drug effects; D005243:Feces / Q000382:microbiology; D006801:Humans; D007421:Intestine, Small / Q000382:microbiology; D008099:Liver / Q000382:microbiology; D051379:Mice; D010455:Peptides / Q000138:chemical synthesis / Q000276:immunology* / Q000302:isolation & purification; D012486:Salmonella typhimurium / Q000187:drug effects; D000685:Serum Amyloid A Protein / Q000138:chemical synthesis / Q000276:immunology* / Q000302:isolation & purification
chemical_list: D010455:Peptides; C489625:SAA3P protein, human; D000685:Serum Amyloid A Protein