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Heparan sulfate proteoglycans mediate Staphylococcus aureus interactions with intestinal epithelium

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Abstract

Staphylococcus aureus can be internalized by non-professional phagocytes, and may colonize the intestine in normal and antibiotic-treated individuals. Intestinal colonization may depend on the interactions of S. aureus with the intestinal epithelium. The best described mechanism of S. aureus binding to eukaryotic cells involves S. aureus fibronectin binding proteins (FnBPs), using fibronectin as a bridging molecule to β1 integrins on the eukaryotic cell surface. Because S. aureus can be internalized by enterocytes, and because S. aureus is known to bind heparan sulfate (HS), we hypothesized that heparan sulfate proteoglycans (HSPGs) widely expressed on epithelia may mediate S. aureus interactions with intestinal epithelial cells. Internalization of S. aureus RN6390 by cultured intestinal epithelial cells was inhibited in a dose-dependent fashion by the HS mimic heparin, and by HS itself. Internalization of S. aureus DU5883, which lacks expression of staphylococcal FnBPs, was also inhibited by heparin. S. aureus adherence to ARH-77 cells, transfected to express the HSPG syndecan-1, was greatly increased when compared to adherence to plasmid control ARH-77 cells which have little detergent extractable HS. In addition, compared to wild-type HS-expressing Chinese hamster ovary (CHO) cells, internalization of S. aureus was decreased using mutant CHO cells with decreased HS expression. These findings are consistent with a model wherein S. aureus internalization by intestinal epithelial cells (and perhaps other epithelia) is mediated by S. aureus binding to the HS moiety of cell-surface HSPGs, and this interaction appears independent of fibronectin binding.

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Acknowledgements

This work was supported by U.S. Public Health Service grants AI 49686 (DH) and GM 066751 (CW) from the National Institutes of Health.

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Authors and Affiliations

  1. Department of Laboratory Medicine and Pathology, University of Minnesota, Mayo Mail Code 609, 420 Delaware Street, SE, Minneapolis, MN, 55455, USA

    Carol L. Wells

  2. Department of Surgery, University of Minnesota, Minneapolis, MN, 55455, USA

    Donavon J. Hess

  3. Department of Genetics, Cell biology and Development, University of Minnesota, Minneapolis, MN, 55455, USA

    Michelle J. Henry-Stanley & Stanley L. Erlandsen

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  1. Donavon J. Hess
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  2. Michelle J. Henry-Stanley
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Correspondence to Carol L. Wells.

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Hess, D.J., Henry-Stanley, M.J., Erlandsen, S.L. et al. Heparan sulfate proteoglycans mediate Staphylococcus aureus interactions with intestinal epithelium. Med Microbiol Immunol 195, 133–141 (2006). https://doi.org/10.1007/s00430-005-0007-5

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