Molecular analysis of the role of the group A streptococcal cysteine protease, hyaluronic acid capsule, and M protein in a murine model of human invasive soft-tissue infection
Molecular analysis of the role of the group A streptococcal cysteine protease, hyaluronic acid capsule, and M protein in a murine model of human invasive soft-tissue infection
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DOI：
10.1172/jci3065
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发表时间：
1998-08-01
影响因子：
15.9
通讯作者：
Wessels, MR
中科院分区：
文献类型：
--
作者：
Ashbaugh, CD;Warren, HB;Wessels, MR
由A组链球菌引起的人类侵袭性软组织感染与显著的发病率和死亡率相关。为了研究这些严重感染的发病机制，我们在人类侵袭性软组织感染的小鼠模型中，用从坏死性筋膜炎患者中回收的M-3型分离株或缺乏半胱氨酸蛋白酶、透明质酸囊或M蛋白的同基因置换突变体表征宿主对细菌挑战的反应。用野生型或半胱氨酸蛋白酶缺陷型菌株攻毒的动物在接种部位出现扩散性组织坏死，出现菌血症，随后死亡。坏死病灶的组织学检查显示细菌遍布发炎的皮下组织。皮下层的小动脉和小静脉血栓形成，覆盖的组织梗死。相比之下，无论是无囊或M蛋白缺陷突变体的动物挑战开发了一个组织肿胀的焦点区域在接种部位没有坏死或随后的全身性疾病。组织病理学检查的软组织病变证实细菌局限在一个良好的皮下脓肿。我们的结论是，A组链球菌透明质酸胶囊和M蛋白，但不是半胱氨酸蛋白酶，是至关重要的发展组织坏死，继发菌血症，和致命的感染，在小鼠模型的人坏死性筋膜炎。
Human invasive soft-tissue infections caused by group A Streptococcus are associated with significant morbidity and mortality. To investigate the pathogenesis of these serious infections, we characterized the host response to bacterial challenge with an M-type 3 isolate recovered from a patient with necrotizing fasciitis, or with isogenic gene replacement mutants deficient in cysteine protease, hyaluronic acid capsule, or M protein in a murine model of human invasive soft-tissue infection. Animals challenged with the wild-type or cysteine protease-deficient strain developed spreading tissue necrosis at the site of inoculation, became bacteremic, and subsequently died. Histopathologic examination of the necrotic lesion revealed bacteria throughout inflamed subcutaneous tissue. Arterioles and venules in the subcutaneous layer were thrombosed and the overlying tissue was infarcted. In contrast, animals challenged with either an acapsular or M protein-deficient mutant developed a focal area of tissue swelling at the site of inoculation without necrosis or subsequent systemic disease. Histopathologic examination of the soft-tissue lesion demonstrated bacteria confined within a well-formed subcutaneous abscess. We conclude that the group A streptococcal hyaluronic acid capsule and M protein, but not the cysteine protease, are critical for the development of tissue necrosis, secondary bacteremia, and lethal infection in a murine model of human necrotizing fasciitis.