Department of Immunology, Institute of Biomedical Sciences.
J Infect Dis. 2014 Mar;209(6):876-86. doi: 10.1093/infdis/jit569. Epub 2013 Oct 26.
Leptospirosis is an infectious disease of public health importance. To successfully colonize the host, pathogens have evolved multiple strategies to escape the complement system. Here we demonstrate that the culture supernatant of pathogenic but not saprophytic Leptospira inhibit the three complement pathways. We showed that the proteolytic activity in the supernatants of pathogenic strains targets the central complement molecule C3 and specific proteins from each pathway, such as factor B, C2, and C4b. The proteases cleaved α and β chains of C3 and work in synergy with host regulators to inactivate C3b. Proteolytic activity was inhibited by 1,10-phenanthroline, suggesting the participation of metalloproteases. A recombinant leptospiral metalloprotease from the thermolysin family cleaved C3 in serum and could be one of the proteases responsible for the supernatant activity. We conclude that pathogenic leptospiral proteases can deactivate immune effector molecules and represent potential targets to the development of new therapies in leptospirosis.
钩端螺旋体病是一种具有重要公共卫生意义的传染病。为了成功定殖宿主，病原体进化出多种策略来逃避补体系统。在这里，我们证明了致病性而非腐生性钩端螺旋体的培养上清液抑制了三条补体途径。我们表明，致病性菌株上清液中的蛋白水解活性针对中央补体分子 C3 以及每条途径的特定蛋白，如因子 B、C2 和 C4b。蛋白酶切割 C3 的α和β链，并与宿主调节剂协同作用使 C3b 失活。蛋白水解活性被 1,10-菲咯啉抑制，提示金属蛋白酶的参与。来自热稳定丝氨酸蛋白酶家族的重组钩端螺旋体金属蛋白酶在血清中切割 C3，可能是负责上清液活性的蛋白酶之一。我们得出结论，致病性钩端螺旋体蛋白酶可以使免疫效应分子失活，是钩端螺旋体病新疗法开发的潜在靶点。
