Non-anticoagulant heparin as a pre-exposure prophylaxis prevents Lyme disease infection
Loading...
Authors
Lin, Yi Pin
Yu, Yanlei
Marcinkiewicz, Ashley L.
Lederman, Patricia
Hart, Thomas M.
Zhang, Fuming
Linhardt, Robert J.
Issue Date
2020-03-13
Type
Article
Language
ENG
Keywords
Biology , Chemistry and chemical biology , Chemical and biological engineering , Biomedical engineering
Alternative Title
Abstract
Lyme 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.
Description
ACS Infectious Diseases, 6, 503−514
Note : 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.
Note : 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.
Full Citation
Non-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.
Publisher
American Chemical Society (ACS)
Terms of Use
Journal
Volume
Issue
PubMed ID
DOI
ISSN
23738227