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.
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.
Gardiner
Gillian E
GE
Teagasc, Moorepark Food Research Center, Fermoy Co, Cork, Ireland. ggardiner@wit.ie
O'Flaherty
Sarah
S
Casey
Pat G
PG
Weber
Annika
A
McDonald
Thomas L
TL
Cronin
Michael
M
Hill
Colin
C
Ross
Reynolds P
RP
Gahan
Cormac G M
CG
Shanahan
Fergus
F
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
D010455:Peptides; C489625:SAA3P protein, human; D000685:Serum Amyloid A Protein