Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA.
Expert Rev Mol Med. 2010 Feb 1;12:e5. doi: 10.1017/S1462399409001367.
Many microbial pathogens subvert proteoglycans for their adhesion to host tissues, invasion of host cells, infection of neighbouring cells, dissemination into the systemic circulation, and evasion of host defence mechanisms. Where studied, specific virulence factors mediate these proteoglycan-pathogen interactions, which are thus thought to affect the onset, progression and outcome of infection. Proteoglycans are composites of glycosaminoglycan (GAG) chains attached covalently to specific core proteins. Proteoglycans are expressed ubiquitously on the cell surface, in intracellular compartments, and in the extracellular matrix. GAGs mediate the majority of ligand-binding activities of proteoglycans, and many microbial pathogens elaborate cell-surface and secreted factors that interact with GAGs. Some pathogens also modulate the expression and function of proteoglycans through known virulence factors. Several GAG-binding pathogens can no longer attach to and invade host cells whose GAG expression has been reduced by mutagenesis or enzymatic treatment. Furthermore, GAG antagonists have been shown to inhibit microbial attachment and host cell entry in vitro and reduce virulence in vivo. Together, these observations underscore the biological significance of proteoglycan-pathogen interactions in infectious diseases.
许多微生物病原体通过糖胺聚糖（GAG）链与特定核心蛋白的共价连接来修饰蛋白聚糖，从而实现对宿主组织的黏附、宿主细胞的入侵、邻近细胞的感染、进入全身循环以及逃避宿主防御机制。在已研究的情况下，特定的毒力因子介导这些蛋白聚糖-病原体相互作用，因此被认为会影响感染的发生、进展和结果。蛋白聚糖是糖胺聚糖（GAG）链附着到特定核心蛋白上的复合物。蛋白聚糖在细胞表面、细胞内区室和细胞外基质中广泛表达。GAG 介导了蛋白聚糖大多数配体结合活性，许多微生物病原体产生细胞表面和分泌因子，与 GAG 相互作用。一些病原体还通过已知的毒力因子来调节蛋白聚糖的表达和功能。通过突变或酶处理降低 GAG 表达后，一些 GAG 结合病原体就不能再附着和侵入宿主细胞。此外，已证明 GAG 拮抗剂在体外可抑制微生物的附着和宿主细胞的进入，并降低体内的毒力。这些观察结果共同强调了蛋白聚糖-病原体相互作用在传染病中的生物学意义。
