Duensing T D, Wing J S, van Putten J P
Laboratory of Microbial Structure and Function, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana 59840, USA.
Infect Immun. 1999 Sep;67(9):4463-8. doi: 10.1128/IAI.67.9.4463-4468.1999.
Fundamental to the virulence of microbial pathogens is their capacity for adaptation and survival within variable, and often hostile, environments encountered in the host. We describe a novel, extragenomic mechanism of surface modulation which may amplify the adaptive and pathogenic potential of numerous bacterial species, including Staphylococcus, Yersinia, and pathogenic Neisseria species, as well as Helicobacter pylori and Streptococcus pyogenes. The mechanism involves specific bacterial recruitment of heparin, glycosaminoglycans, or related sulfated polysaccharides, which in turn serve as universal binding sites for a diverse array of mammalian heparin binding proteins, including adhesive glycoproteins (vitronectin and fibronectin), inflammatory (MCP-3, PF-4, and MIP-1alpha) and immunomodulatory (gamma interferon) intermediates, and fibroblast growth factor. This strategy impacts key aspects of microbial pathogenicity as exemplified by increased bacterial invasion of epithelial cells and inhibition of chemokine-induced chemotaxis. Our findings illustrate a previously unrecognized form of parasitism that complements classical virulence strategies encoded within the microbial genome.
微生物病原体毒力的基础在于它们在宿主中遇到的多变且通常具有敌意的环境中适应和生存的能力。我们描述了一种新的基因组外表面调节机制，它可能增强包括葡萄球菌、耶尔森菌、致病性奈瑟菌属，以及幽门螺杆菌和化脓性链球菌在内的众多细菌物种的适应和致病潜力。该机制涉及细菌对肝素、糖胺聚糖或相关硫酸化多糖的特异性募集，这些多糖继而作为多种哺乳动物肝素结合蛋白的通用结合位点，包括黏附糖蛋白（玻连蛋白和纤连蛋白）、炎症介质（单核细胞趋化蛋白-3、血小板因子4和巨噬细胞炎性蛋白-1α）和免疫调节因子（γ干扰素），以及成纤维细胞生长因子。这一策略影响微生物致病性的关键方面，例如细菌对上皮细胞侵袭的增加以及趋化因子诱导的趋化作用的抑制。我们的发现阐明了一种以前未被认识的寄生形式，它补充了微生物基因组中编码的经典毒力策略。
