Lin Yi-Pin, Li Lingyun, Zhang Fuming, Linhardt Robert J
Department of Biomedical Science, State University of New York at Albany, Albany, NY, USA.
Division of Infectious Disease, Wadsworth Center, New York State Department of Health, Albany, NY, USA.
Microbiology (Reading). 2017 Dec;163(12):1759-1766. doi: 10.1099/mic.0.000571. Epub 2017 Nov 8.
The spirochete bacterium Borrelia burgdorferi sensu lato is the causative agent of Lyme disease, the most common vector-borne disease in Europe and the United States. The spirochetes can be transmitted to humans via ticks, and then spread to different tissues, leading to arthritis, carditis and neuroborreliosis. Although antibiotics have commonly been used to treat infected individuals, some treated patients do not respond to antibiotics and experience persistent, long-term arthritis. Thus, there is a need to investigate alternative therapeutics against Lyme disease. The spirochete bacterium colonization is partly attributed to the binding of the bacterial outer-surface proteins to the glycosaminoglycan (GAG) chains of host proteoglycans. Blocking the binding of these proteins to GAGs is a potential strategy to prevent infection. In this review, we have summarized the recent reports of B. burgdorferi sensu lato GAG-binding proteins and discussed the potential use of synthetic and semi-synthetic compounds, including GAG analogues, to block pathogen interaction with GAGs. Such information should motivate the discovery and development of novel GAG analogues as new therapeutics for Lyme disease. New therapeutic approaches should eventually reduce the burden of Lyme disease and improve human health.
疏螺旋体伯氏疏螺旋体狭义种是莱姆病的病原体，莱姆病是欧美最常见的媒介传播疾病。螺旋体可通过蜱虫传播给人类，然后扩散到不同组织，导致关节炎、心脏炎和神经莱姆病。尽管抗生素通常用于治疗感染者，但一些接受治疗的患者对抗生素无反应，并经历持续性的长期关节炎。因此，有必要研究针对莱姆病的替代疗法。螺旋体细菌的定植部分归因于细菌外表面蛋白与宿主蛋白聚糖的糖胺聚糖（GAG）链的结合。阻断这些蛋白与GAG的结合是预防感染的一种潜在策略。在本综述中，我们总结了狭义伯氏疏螺旋体GAG结合蛋白的最新报道，并讨论了合成和半合成化合物（包括GAG类似物）在阻断病原体与GAG相互作用方面的潜在用途。此类信息应能推动新型GAG类似物的发现和开发，作为莱姆病的新疗法。新的治疗方法最终应能减轻莱姆病的负担并改善人类健康。
