Svensson Mikael D, Sjöbring Ulf, Luo Feng, Bessen Debra E
Department of Laboratory Medicine, Lund University, Lund, Sweden1.
Department of Ecology and Evolutionary Biology, Yale University, 165 Prospect Street, New Haven, CT, USA2.
Microbiology (Reading). 2002 Dec;148(Pt 12):3933-3945. doi: 10.1099/00221287-148-12-3933.
Primary infection by group A streptococci (GAS) takes place at either the throat or skin of the human host, often leading to pharyngitis or impetigo, respectively. Many GAS strains differ in their preference for throat and skin tissue sites. Previous epidemiological findings show that many of the strains displaying strong tropism for the skin have a high-affinity binding site for plasminogen, located within M protein (PAM), a prominent surface fibril. Plasminogen bound by PAM interacts with streptokinase, a plasminogen activator secreted by GAS, to yield bacterial-bound plasmin activity. In this study, PAM and streptokinase were tested for their roles in infection using an experimental model that closely mimics human impetigo. Inactivation of genes encoding either PAM or streptokinase led to a partial, but significant, loss of virulence in vivo, as measured by net growth of the bacteria and pathological alterations. The relative loss in virulence in vivo was greater for the streptokinase mutant than for the PAM mutant. However, the PAM mutant, but not the streptokinase mutant, displayed a partial loss in resistance to phagocytosis in vitro. The combined experimental and epidemiological data provide evidence that PAM and streptokinase play a key role in mediating skin-specific infection by GAS. In addition, secreted cysteine proteinase activity due to SpeB leads to degradation of streptokinase in stationary phase broth cultures. Since SpeB is also a determinant of tissue-specific GAS infection at the skin, direct interactions between these two proteolytic pathways may constitute an important pathogenic mechanism. An integrated model for superficial infection at the skin is presented.
A 组链球菌（GAS）的原发性感染发生在人类宿主的咽喉或皮肤，通常分别导致咽炎或脓疱病。许多 GAS 菌株对咽喉和皮肤组织部位的偏好不同。先前的流行病学研究结果表明，许多对皮肤表现出强烈嗜性的菌株在 M 蛋白（PAM）（一种突出的表面纤维）内具有纤溶酶原的高亲和力结合位点。与 PAM 结合的纤溶酶原与 GAS 分泌的纤溶酶原激活剂链激酶相互作用，产生细菌结合的纤溶酶活性。在本研究中，使用紧密模拟人类脓疱病的实验模型测试了 PAM 和链激酶在感染中的作用。编码 PAM 或链激酶的基因失活导致体内毒力部分但显著丧失，通过细菌的净生长和病理改变来衡量。链激酶突变体在体内的毒力相对丧失比 PAM 突变体更大。然而，PAM 突变体而非链激酶突变体在体外对吞噬作用的抵抗力出现部分丧失。综合实验和流行病学数据提供了证据，表明 PAM 和链激酶在介导 GAS 的皮肤特异性感染中起关键作用。此外，由于 SpeB 导致的分泌性半胱氨酸蛋白酶活性在稳定期肉汤培养物中导致链激酶降解。由于 SpeB 也是皮肤组织特异性 GAS 感染的决定因素，这两种蛋白水解途径之间的直接相互作用可能构成一种重要的致病机制。本文提出了一个皮肤浅表感染的综合模型。
