Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Curr Opin Hematol. 2019 Sep;26(5):343-348. doi: 10.1097/MOH.0000000000000527.
Fibrin(ogen) is a multifunctional clotting protein that not only has critical roles in hemostasis but is also important in inflammatory processes that control bacterial infection. As a provisional extracellular matrix protein, fibrin(ogen) functions as a physical barrier, a scaffold for immune cell migration, or as a spatially-defined cue to drive inflammatory cell activation. These mechanisms contribute to overall host antimicrobial defense against infection. However, numerous bacterial species have evolved mechanisms to manipulate host fibrin(ogen) to promote microbial virulence and survival. Staphylococcal species, in particular, express numerous virulence factors capable of engaging fibrin(ogen), promoting fibrin formation, and driving the dissolution of fibrin matrices.
Recent studies have highlighted both new insights into the molecular mechanisms involved in fibrin(ogen)-mediated host defense and pathogen-driven virulence. Of particular interest is the role of fibrin(ogen) in forming host protective biofilms versus pathogen protective barriers and biofilms as well as the role of fibrin(ogen) in mediating direct host antimicrobial responses.
Current data suggest that the role of fibrin(ogen) in staphylococcal infection is highly context-dependent and that better defining the precise cellular and molecular pathways activated will provide unique opportunities of therapeutic intervention to better treat Staphylococcal disease.
纤维蛋白原是一种多功能的凝血蛋白，它不仅在止血中起着关键作用，而且在控制细菌感染的炎症过程中也很重要。作为一种临时的细胞外基质蛋白，纤维蛋白原起着物理屏障的作用、免疫细胞迁移的支架，或者作为一个空间限定的信号来驱动炎症细胞的激活。这些机制有助于宿主对抗感染的整体抗菌防御。然而，许多细菌物种已经进化出操纵宿主纤维蛋白原的机制，以促进微生物的毒力和存活。葡萄球菌属的物种，特别是，表达了许多能够与纤维蛋白原结合、促进纤维蛋白形成并驱动纤维蛋白基质溶解的毒力因子。
最近的研究强调了纤维蛋白原介导的宿主防御和病原体驱动的毒力中涉及的分子机制的新见解。特别有趣的是纤维蛋白原在形成宿主保护性生物膜与病原体保护性屏障和生物膜中的作用，以及纤维蛋白原在介导直接宿主抗微生物反应中的作用。
目前的数据表明，纤维蛋白原在葡萄球菌感染中的作用高度依赖于上下文，更好地定义激活的精确细胞和分子途径将为治疗葡萄球菌病提供独特的治疗干预机会。
