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.

中文翻译：

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非抗凝素肝素可预防接触前预防莱姆病的感染。

莱姆病（LD）由螺旋体疏螺旋体伯氏疏螺旋体（Bbsl）引起。通过tick传播给人类后，Bbs1传播到多个器官，导致关节炎，心脏病和神经硼尿病。目前尚无有效的预防tick暴露前人类LD的方法。因此，需要针对LD的暴露前预防（PrEP）。LD细菌在不同部位的建立部分取决于Bbs1与组织中的蛋白聚糖（PGs）和糖胺聚糖（GAGs）的结合。药物肝素在结构上与这些GAG相似，并抑制Bbs1与PG，GAG，细胞和组织的附着，表明其具有预防LD的潜力。但是，肝素的抗凝活性经常导致出血，阻碍了该化合物作为LD PrEP的发展。我们之前已经合成了非抗凝型肝素（NACH），已在小鼠和人类中进行了安全性验证。在这里，我们表明NACH阻止Bbs1与PG，GAG和哺乳动物细胞的附着。我们还发现，在暴露于带有Bbs1的壁虱之前先用NACH处理小鼠，然后连续施用该化合物可防止Bbs1引起的组织定植。此外，在感染的早期阶段，用NACH处理的小鼠会产生更高水平的针对Bbs1的IgG和IgM，这表明抗体免疫反应的上调可能是NACH介导的LD预防的机制之一。这是最早研究基于肝素的化合物在tick暴露前预防LD的能力的研究之一。所提供的信息也可能会扩展为预防其他传染病媒介。