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dc.contributor.authorLin, Yi Pin
dc.contributor.authorYu, Yanlei
dc.contributor.authorMarcinkiewicz, Ashley L.
dc.contributor.authorLederman, Patricia
dc.contributor.authorHart, Thomas M.
dc.contributor.authorZhang, Fuming
dc.contributor.authorLinhardt, Robert J.
dc.date2020
dc.date.accessioned2022-06-23T04:45:59Z
dc.date.available2022-06-23T04:45:59Z
dc.date.issued2020-03-13
dc.identifier.citationNon-anticoagulant heparin as a pre-exposure prophylaxis prevents Lyme disease infection, Y.-P. Lin, , Y. Yu, A. Marcinkiewicz, P. Lederman, T. Hart, F. Zhang, R. J. Linhardt, ACS Infectious Diseases,6, 503−514, 2020.
dc.identifier.issn23738227
dc.identifier.urihttps://hdl.handle.net/20.500.13015/5396
dc.identifier.urihttps://doi.org/10.1021/acsinfecdis.9b00425
dc.descriptionACS Infectious Diseases, 6, 503−514
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.abstractLyme disease (LD) is caused by the spirochete Borrelia burgdorferi sensu lato (Bbsl). After transmission to humans by ticks, Bbsl spreads to multiple organs, leading to arthritis, carditis, and neuroborreliosis. No effective prophylaxis against human LD prior to tick exposure is currently available. Thus, a pre-exposure prophylaxis (PrEP) against LD is needed. The establishment of LD bacteria at diverse sites is dictated partly by the binding of Bbsl to proteoglycans (PGs) and glycosaminoglycans (GAGs) in tissues. The drug heparin is structurally similar to these GAGs and inhibits Bbsl attachment to PGs, GAGs, cells, and tissues, suggesting its potential to prevent LD. However, the anticoagulant activity of heparin often results in hemorrhage, hampering the development of this compound as LD PrEP. We have previously synthesized a non-anticoagulant version of heparin (NACH), which was verified for safety in mice and humans. Here, we showed that NACH blocks Bbsl attachment to PGs, GAGs, and mammalian cells. We also found that treating mice with NACH prior to the exposure of ticks carrying Bbsl followed by continuous administration of this compound prevents tissue colonization by Bbsl. Furthermore, NACH-treated mice develop greater levels of IgG and IgM against Bbsl at early stages of infection, suggesting that the upregulation of antibody immune responses may be one of the mechanisms for NACH-mediated LD prevention. This is one of the first studies examining the ability of a heparin-based compound to prevent LD prior to tick exposure. The information presented might also be extended to prevent other infectious diseases agents.
dc.description.sponsorshipNational Science Foundation
dc.languageen_US
dc.language.isoENG
dc.publisherAmerican Chemical Society (ACS)
dc.relation.ispartofThe Linhardt Research Labs Online Collection
dc.relation.ispartofRensselaer Polytechnic Institute, Troy, NY
dc.relation.ispartofACS Infectious Diseases
dc.relation.urihttps://harc.rpi.edu/
dc.subjectBiology
dc.subjectChemistry and chemical biology
dc.subjectChemical and biological engineering
dc.subjectBiomedical engineering
dc.titleNon-anticoagulant heparin as a pre-exposure prophylaxis prevents Lyme disease infection
dc.typeArticle
dcterms.accessRightsA full text version is available in DSpace@RPI
dcterms.isPartOfJournal
dcterms.isVersionOfhttps://doi.org/10.1021/acsinfecdis.9b00425
dc.rights.holderIn Copyright : this Item is protected by copyright and/or related rights. You are free to use this Item in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the rights-holder(s). https://rightsstatements.org/page/InC/1.0/
dc.creator.identifierhttps://orcid.org/0000-0003-2219-5833
dc.relation.departmentThe Linhardt Research Labs.
dc.relation.departmentThe Shirley Ann Jackson, Ph.D. Center for Biotechnology and Interdisciplinary Studies (CBIS)
rpi.description.pages503-514
rpi.description.volume6


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