ABILITY OF THE HEPARAN SULFATE PROTEOGLYCAN SYNDECAN-1 TO PARTICIPATE IN BACTERIAL TRANSLOCATION ACROSS THE INTESTINAL EPITHELIAL BARRIER

Abstract

Although hundreds of microbial species reside in the human intestinal tract, comparatively few (e.g., Escherichia coli and other enterobacteria, Enterococcus faecalis, etc.) are typically associated with systemic infection in postsurgical, shock, and trauma patients. Syndecan-1 is the predominant cell surface heparan sulfate proteoglycan expressed on epithelia, and there is substantial evidence that heparan sulfate participates in interactions of a variety of frankly pathogenic microbes with mammalian cells. To investigate the role of syndecan-1 in interactions of enteric flora with intestinal epithelium, bacteria that might use the enterocyte as a portal of entry for systemic infection (including E. faecalis, E. coli, and other enterobacteria, and several species of staphylococci and streptococci) were studied for their abilities to interact with syndecan-1. Streptococcus bovis, S. agalactiae, S. pyogenes, Staphylococcus aureus, and S. epidermidis showed increased adherence to ARH-77 cells transfected to express syndecan-1. Heparin, a heparan sulfate analog, inhibited internalization of S. bovis, S. agalactiae, S. pyogenes, and S. aureus by HT-29 enterocytes (prominent syndecan-1 expression), but not Caco-2 enterocytes (relatively low syndecan-1 expression). Data from experiments with Chinese hamster ovary cells with altered glycosaminoglycan expression indicated that heparan sulfate and chondroitin sulfate (glycosaminoglycans on the syndecan-1 ectodomain) participated in bacterial interactions with mammalian cells. Thus, although E. faecalis, E. coli, and other gram-negative enterobacteria did not appear to interact with syndecan-1, this heparan sulfate proteoglycan may mediate enterocyte interactions with some staphylococci and streptococci that are known to cause systemic infections in specific populations of high-risk, immunosuppressed, postsurgical, and trauma patients.