Nitzsche Ramona, Rosenheinrich Maik, Kreikemeyer Bernd, Oehmcke-Hecht Sonja
Institute of Medical Microbiology, Virology, and Hygiene, Rostock University Medical Centre, Rostock, Germany
Infect Immun. 2015 Aug;83(8):3035-42. doi: 10.1128/IAI.00180-15.
Severe invasive infectious diseases remain a major and life-threatening health problem. In serious cases, a systemic activation of the coagulation cascade is a critical complication that is associated with high mortality rates. We report here that streptokinase, a group A streptococcal plasminogen activator, triggers the activation of the human contact system. Activation of contact system factors at the surface of the Streptococcus pyogenes serotype M49 is dependent on streptokinase and plasminogen. Our results also show that secreted streptokinase is an efficient contact system activator, independent from a contact surface. This results in the processing of high-molecular-weight kininogen and the release of bradykinin, a potent vascular mediator. We further investigated whether the ability of 50 different clinical S. pyogenes isolates to activate the contact system is associated with an invasive phenotype. The data reveal that isolates from invasive infections trigger an activation of the contact system more potently than strains isolated from noninvasive infections. The present study gives new insights into the mechanisms by which S. pyogenes triggers the human contact system and stresses the function of soluble and surface located plasmin exploited as a group A streptococcal virulence factor through the action of streptokinase.
严重的侵袭性传染病仍然是一个重大且危及生命的健康问题。在严重情况下，凝血级联反应的全身激活是一种关键并发症，与高死亡率相关。我们在此报告，链激酶，一种A组链球菌纤溶酶原激活剂，可触发人类接触系统的激活。化脓性链球菌M49血清型表面的接触系统因子激活依赖于链激酶和纤溶酶原。我们的结果还表明，分泌的链激酶是一种有效的接触系统激活剂，独立于接触表面。这导致高分子量激肽原的加工和缓激肽的释放，缓激肽是一种强效的血管介质。我们进一步研究了50种不同临床化脓性链球菌分离株激活接触系统的能力是否与侵袭性表型相关。数据显示，侵袭性感染分离株比非侵袭性感染分离株更有效地触发接触系统的激活。本研究为化脓性链球菌触发人类接触系统的机制提供了新的见解，并强调了通过链激酶的作用，可溶性和表面定位的纤溶酶作为A组链球菌毒力因子的功能。
