Division of Respiratory Diseases, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Department of Pediatrics, Harvard Medical School, Boston, MA, USA.
Methods Mol Biol. 2022;2303:605-625. doi: 10.1007/978-1-0716-1398-6_46.
Heparan sulfate proteoglycans (HSPGs) are at the forefront of host-microbe interactions. Cell surface HSPGs are thought to promote infection as attachment and internalization receptors for many bacterial pathogens and as soluble inhibitors of host immunity when released from the cell surface by ectodomain shedding. However, the importance of HSPG-pathogen interactions in vivo has yet to be clearly established. Here we describe several representative methods to study the role of HSPGs in systemic bacterial infections, such as bacteremia and sepsis. The overall experimental strategy is to use mouse models to establish the physiological significance of HSPGs, to determine the identity of HSPGs that specifically promote infection, and to define key structural features of HSPGs that enhance bacterial virulence in systemic infections.
硫酸乙酰肝素蛋白聚糖 (HSPGs) 处于宿主-微生物相互作用的前沿。细胞表面 HSPGs 被认为是许多细菌病原体的附着和内化受体，并且当通过细胞表面的蛋白水解脱落从细胞表面释放时，作为宿主免疫的可溶性抑制剂。然而，HSPG-病原体相互作用在体内的重要性尚未得到明确确立。在这里，我们描述了几种研究 HSPGs 在全身细菌感染（如菌血症和败血症）中的作用的代表性方法。总体实验策略是使用小鼠模型来确定 HSPGs 的生理意义，确定特异性促进感染的 HSPGs 的身份，并定义增强全身感染中细菌毒力的 HSPGs 的关键结构特征。
