Campylobacter jejuni Binds Intestinal H(O) Antigen (Fucα1, 2Galβ1, 4GlcNAc), and Fucosyloligosaccharides of Human Milk Inhibit Its Binding and Infection

• Published in: The Journal of biological chemistry 2003-04, Vol.278 (16), p.14112-14120
• Main Authors: Ruiz-Palacios, Guillermo M., Cervantes, Luz Elena, Ramos, Pilar, Chavez-Munguia, Bibiana, Newburg, David S.
• Format: Article
• Language: English
• Subjects: ABO Blood-Group System; Animals; Antigens - chemistry; Campylobacter jejuni - metabolism; Cell Adhesion; CHO Cells; Cricetinae; Dose-Response Relationship, Drug; Epitopes; Fucose - metabolism; Fucosyltransferases - chemistry; Fucosyltransferases - genetics; Fucosyltransferases - metabolism; Galactoside 2-alpha-L-fucosyltransferase; Humans; Inhibitory Concentration 50; Lectins - metabolism; Ligands; Mice; Mice, Inbred BALB C; Microscopy, Fluorescence; Milk, Human - metabolism; Neurons - microbiology; O Antigens - chemistry; Oligosaccharides - chemistry; Polysaccharides - chemistry; Protein Binding; Time Factors; Transfection
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M207744200

The most common cause of infant mortality is diarrhea; the most common cause of bacterial diarrhea isCampylobacter jejuni, which is also the primary cause of motor neuron paralysis. The first step in campylobacter pathogenesis is adherence to intestinal mucosa. We found that such binding was inhibited in vitro by human milk and, with high avidity, by α1,2-fucosylated carbohydrate moieties containing the H(O) blood group epitope (Fucα1,2Galβ1,4GlcNAc … ). In studies on the mechanism of adherence, campylobacter, which normally does not bind to Chinese hamster ovary cells, bound avidly when the cells were transfected with a human α1,2-fucosyltransferase gene that caused overexpression of H-2 antigen; binding was specifically inhibited by H-2 ligands (lectins Ulex europaeus and Lotus tetragonolobus and H-2 monoclonal antibody), H-2 mimetics, and human milk oligosaccharides. Human milk oligosaccharides inhibited campylobacter colonization of mice in vivo and human intestinal mucosa ex vivo. Campylobacter colonization of nursing mouse pups was inhibited if their dams had been transfected with a human α1,2-fucosyltransferase gene that caused expression of H(O) antigen in milk. We conclude that campylobacter binding to intestinal H-2 antigen is essential for infection. Milk fucosyloligosaccharides and specific fucosyl α1,2-linked molecules inhibit this binding and may represent a novel class of antimicrobial agents.