Identification of a transcytosis epitope on staphylococcal enterotoxins.
Staphylococcal enterotoxins (SE) are exoproteins produced by Staphylococcus aureus that act as superantigens and have been implicated as a leading cause of food-borne disease and toxic shock. Little is known about how these molecules penetrate the gut lining and gain access to both local and systemic immune tissues. To model movement in vitro of staphylococcal enterotoxins, we have employed a monolayer system composed of crypt-like human colonic T-84 cells. SEB and SEA showed comparable dose-dependent transcytosis in vitro, while toxic shock syndrome toxin (TSST-1) exhibited increased movement at lower doses. Synthetic peptides corresponding to specific regions of the SEB molecule were tested in vitro to identify the domain of the protein involved in the transcytosis of SE. A toxin peptide of particular interest contains the amino acid sequence KKKVTAQELD, which is highly conserved across all SE. At a toxin-to-peptide ratio of 1:10, movement of SEB across the monolayers was reduced by 85%. Antisera made against the SEB peptide recognized native SEB and also inhibited SEB transcytosis. Finally, the conserved 10-amino-acid peptide inhibited transcytosis of multiple staphylococcal enterotoxins, SEA, SEE, and TSST-1. These data demonstrate that this region of the staphylococcal enterotoxins plays a distinct role in toxin movement across epithelial cells. It has implications for the prevention of staphylococcal enterotoxin-mediated disease by design of a peptide vaccine that could reduce systemic exposure to oral or inhaled superantigens. Since the sequence identified is highly conserved, it allows for a single epitope blocking the transcytosis of multiple SE.
Shupp
Jeffrey W
JW
Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, Maryland 20742, USA.
Jett
Marti
M
Pontzer
Carol H
CH
D000818:Animals; D001692:Biological Transport; D002460:Cell Line; D004768:Enterotoxins / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D000939:Epitopes; D006801:Humans; D007106:Immune Sera / Q000276:immunology; D007413:Intestinal Mucosa / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL
D004768:Enterotoxins; D000939:Epitopes; D007106:Immune Sera; C026066:enterotoxin A, Staphylococcal; C031818:enterotoxin B, staphylococcal