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dc.rights.licenseCC BY — Creative Commons Attribution
dc.contributor.authorHayashida, A.
dc.contributor.authorAmano, S.
dc.contributor.authorGallo, R.L.
dc.contributor.authorLinhardt, Robert J.
dc.contributor.authorLiu, J.
dc.contributor.authorPark, P.W.
dc.identifier.citation2-O-Sulfated domains in syndecan-1 heparan sulfate inhibit neutrophil cathelicidin and promote S. aureus corneal infection, A. Hayashida, S. Amano, R. L. Gallo, R. J. Linhardt, J. Liu, P.-W. Park, Journal of Biological Chemistry, 290, 16157–16167, 2015.
dc.descriptionJournal of Biological Chemistry, 290, 16157–16167
dc.descriptionNote : if this item contains full text it may be a preprint, author manuscript, or a Gold OA copy that permits redistribution with a license such as CC BY. The final version is available through the publisher’s platform.
dc.description.abstractAblation of syndecan-1 in mice is a gain of function mutation that enables mice to significantly resist infection by several bacterial pathogens. Syndecan-1 shedding is induced by bacterial virulence factors, and inhibition of shedding attenuates bacterial virulence, whereas administration of purified syndecan-1 ectodomain enhances virulence, suggesting that bacteria subvert syndecan-1 ectodomains released by shedding for their pathogenesis. However, the pro-pathogenic functions of syndecan-1 ectodomain have yet to be clearly defined. Here, we examined how syndecan-1 ectodomain enhances Staphylococcus aureus virulence in injured mouse corneas. We found that syndecan-1 ectodomain promotes S. aureus corneal infection in an HS-dependent manner. Surprisingly, we found that this pro-pathogenic activity is dependent on 2-O-sulfated domains in HS, indicating that the effects of syndecan-1 ectodomain are structure-based. Our results also showed that purified syndecan-1 ectodomain and heparan compounds containing 2-O-sulfate motifs inhibit S. aureus killing by antimicrobial factors secreted by degranulated neutrophils, but does not affect intracellular phagocytic killing by neutrophils. Immunodepletion of antimicrobial factors with staphylocidal activities demonstrated that CRAMP, a cationic antimicrobial peptide, is primarily responsible for S. aureus killing among other factors secreted by degranulated neutrophils. Furthermore, we found that purified syndecan-1 ectodomain and heparan compounds containing 2-O-sulfate units potently and specifically inhibit S. aureus killing by synthetic CRAMP. These results provide compelling evidence that a specific subclass of sulfate groups, and not the overall charge of HS, permits syndecan-1 ectodomains to promote S. aureus corneal infection by inhibiting a key arm of neutrophil host defense.
dc.publisherThe American Society for Biochemistry and Molecular Biology (ASBMB) and Elsevier
dc.relation.ispartofThe Linhardt Research Labs Online Collection
dc.relation.ispartofRensselaer Polytechnic Institute, Troy, NY
dc.rightsAttribution 3.0 United States*
dc.subjectChemistry and chemical biology
dc.subjectChemical and biological engineering
dc.subjectBiomedical engineering
dc.title2-O-Sulfated domains in syndecan-1 heparan sulfate inhibit neutrophil cathelicidin and promote S. aureus corneal infectionen_US
dcterms.accessRightsOpen Access
dcterms.accessRightsA full text version is available in DSpace@RPI
dc.rights.holderCC BY : this license allows reusers to distribute, remix, adapt, and build upon the material in any medium or format, so long as attribution is given to the creator. The license allows for commercial use. Credit must be given to the authors and the original work must be properly cited.
dc.relation.departmentThe Linhardt Research Labs.
dc.relation.departmentThe Shirley Ann Jackson, Ph.D. Center for Biotechnology and Interdisciplinary Studies (CBIS)

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