Effect of deoxymannojirimycin and Brefeldin A on Yersinia pseudotuberculosis invasin--eukaryotic cell interaction.
The cell surface receptors of the Yersinia pseudotuberculosis invasin protein are the alpha 3-6 beta 1 integrins. Invasin and the extracellular matrix protein fibronectin bind to the same or closely located sites on alpha 5 beta 1 integrin, although invasin bind with a much greater affinity. Invasin-integrin interaction promotes bacterial penetration into eukaryotic cells. Binding of fibronectin to its integrin receptor seems to be dependent on terminal oligosaccharides processing. In this paper, we have examined the effect of 1-deoxymannojirimycin (dMNJ), an inhibitor of Golgi alpha-mannosidases involved in processing of N-glycan precursors, and of Brefeldin A (BFA), a natural product of fungi which has profound effects on the structure and function of the Golgi apparatus, on invasin-cell interaction. We found that unlike fibronectin, the interaction of invasin with cells was resistance to dMNJ. However, preincubating cells with BFA caused a dose dependent inhibition of invasin-mediated cell entry, while cell invasion by Salmonella typhimurium was not affected.
Frankel
G
G
Department of Biochemistry, Imperial College of Science, Technology and Medicine, London, U.K.
Gil
S
S
Dougan
G
G
D017485:1-Deoxynojirimycin / Q000494:pharmacology*; D018829:Adhesins, Bacterial; D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism*; D020126:Brefeldin A; D016466:CHO Cells; D002448:Cell Adhesion; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D006224:Cricetinae; D003517:Cyclopentanes / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004847:Epithelial Cells; D004926:Escherichia coli; D005353:Fibronectins / Q000378:metabolism; D006056:Golgi Apparatus / Q000187:drug effects; D006801:Humans; D039201:Integrin alpha3beta1; D039121:Integrin alpha6beta1; D016023:Integrins / Q000378:metabolism; D008361:Mannosidases / Q000037:antagonists & inhibitors; D008969:Molecular Sequence Data; D009844:Oligosaccharides / Q000378:metabolism; D015011:Yersinia pseudotuberculosis / Q000472:pathogenicity*; D043323:alpha-Mannosidase
D018829:Adhesins, Bacterial; D001426:Bacterial Proteins; D003517:Cyclopentanes; D004791:Enzyme Inhibitors; D005353:Fibronectins; D039201:Integrin alpha3beta1; D039121:Integrin alpha6beta1; D016023:Integrins; D009844:Oligosaccharides; C053476:invasin, Yersinia; D017485:1-Deoxynojirimycin; D020126:Brefeldin A; D008361:Mannosidases; D043323:alpha-Mannosidase