Department of Molecular Sciences, The University of Tennessee Health Science Center, 858 Madison Avenue, Memphis, Tennessee 38163, USA.
BMC Microbiol. 2010 Mar 12;10:76. doi: 10.1186/1471-2180-10-76.
Francisella tularensis (FT) is a gram-negative facultative intracellular coccobacillus and is the causal agent of a life-threatening zoonotic disease known as tularemia. Although FT preferentially infects phagocytic cells of the host, recent evidence suggests that a significant number of bacteria can be found extracellularly in the plasma fraction of the blood during active infection. This observation suggests that the interaction between FT and host plasma components may play an important role in survival and dissemination of the bacterium during the course of infection. Plasminogen (PLG) is a protein zymogen that is found in abundance in the blood of mammalian hosts. A number of both gram-positive and gram-negative bacterial pathogens have the ability to bind to PLG, giving them a survival advantage by increasing their ability to penetrate extracellular matrices and cross tissue barriers.
We show that PLG binds to the surface of FT and that surface-bound PLG can be activated to plasmin in the presence of tissue PLG activator in vitro. In addition, using Far-Western blotting assays coupled with proteomic analyses of FT outer membrane preparations, we have identified several putative PLG-binding proteins of FT.
The ability of FT to acquire surface bound PLG that can be activated on its surface may be an important virulence mechanism that results in an increase in initial infectivity, survival, and/or dissemination of this bacterium in vivo.
土拉弗朗西斯菌(FT)是一种革兰氏阴性兼性细胞内球杆菌,是一种危及生命的人畜共患疾病——土拉菌病的病原体。尽管 FT 优先感染宿主的吞噬细胞,但最近的证据表明,在活跃感染期间,血液的血浆部分中可以发现相当数量的细菌存在于细胞外。这一观察结果表明,FT 与宿主血浆成分之间的相互作用可能在感染过程中细菌的存活和传播中发挥重要作用。纤溶酶原(PLG)是一种在哺乳动物宿主血液中大量存在的蛋白酶原。许多革兰氏阳性和革兰氏阴性细菌病原体都有能力与 PLG 结合,通过增加其穿透细胞外基质和穿越组织屏障的能力,从而获得生存优势。
我们表明 PLG 与 FT 的表面结合,并且在存在组织纤溶酶原激活物的情况下,表面结合的 PLG 可以在体外被激活为纤溶酶。此外,通过与 FT 外膜制剂的蛋白质组学分析相结合的远 Western 印迹测定,我们已经鉴定出 FT 的几种潜在的 PLG 结合蛋白。
FT 获得表面结合的 PLG 的能力,并且可以在其表面上被激活,这可能是一种重要的毒力机制,导致该细菌在体内初始感染性、存活和/或传播能力的增加。