Streptolysin S and necrotising infections produced by group G streptococcus
Streptolysin S and necrotising infections produced by group G streptococcus
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DOI：
10.1016/s0140-6736(02)07371-3
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发表时间：
2002-01-12
期刊：
影响因子：
168.9
通讯作者：
Nizet, V
中科院分区：
文献类型：
--
作者：
Humar, D;Datta, V;Nizet, V
我们遇到了3例由溶血G群链球菌引起的严重坏死性软组织感染。由于与A群链球菌引起的侵袭性感染具有很强的临床相似性，我们研究了共享的β -溶血表型与疾病发病机制的潜在联系。方法采用杂交、DNA测序、靶向诱变和互补等方法建立G群链球菌溶血活性的遗传基础。研究了G型链球菌对乙型溶血素在小鼠坏死性感染中的需要量。每个病人都有潜在的医学状况。溶血G群链球菌是唯一从坏死组织中分离出的微生物。G组链球菌的染色体含有a组链球菌sag操纵子编码-溶血素-溶血素S （SLS）的同源基因。G群链球菌中假定的SLS结构基因sagA的靶向诱变消除了β -溶血活性。皮下注射野生型A组链球菌或G组链球菌的小鼠出现炎症性病变，细菌数量高，中性粒细胞浸润明显，组织病理学证据为弥漫性组织坏死。在注射了等基因A组链球菌或G组链球菌sls阴性突变体的小鼠中没有发现这些变化。在有潜在疾病的患者中，溶血型G群链球菌可产生与A群链球菌相似的坏死性软组织感染。G组链球菌的β -溶血表型是由外毒素SLS产生的，由a组链球菌sag操纵子的9个基因的功能同源物编码。SLS表达参与链球菌坏死性软组织感染的发病机制。
Background We encountered three patients with severe necrotising soft tissue infections due to beta-haemolytic group G streptococcus. Due to strong clinical similarities with invasive infections produced by group A streptococcus, we investigated a potential link of shared beta-haemolytic phenotype to disease pathogenesis.Methods Hybridisation, DNA sequencing, targeted mutagenesis, and complementation studies were used to establish the genetic basis for group G streptococcus beta-haemolytic activity. The requirement of group G streptococcus beta-haemolysin in producing necrotising infection was examined in mice.Findings Each patient had an underlying medical condition. beta-haemolytic group G streptococcus was the sole microbial isolate from debrided necrotic tissue. The group G streptococcus chromosome contained a homologue of the nine-gene group A streptococcus sag operon encoding the beta-haemolysin streptolysin S (SLS). Targeted mutagenesis of the putative SLS structural gene sagA in group G streptococcus eliminated beta-haemolytic activity. Mice injected subcutaneously with wild-type group A streptococcus or group G streptococcus developed an inflammatory lesion with high bacterial counts, marked neutrophil infiltration, and histopathological evidence of diffuse tissue necrosis. These changes were not found in mice injected with the isogenic group A streptococcus or group G streptococcus SLS-negative mutants.Interpretation In patients with underlying medical conditions, beta-haemolytic group G streptococcus can produce necrotising soft tissue infections resembling those produced by group A streptococcus. The beta-haemolytic phenotype of group G streptococcus is produced by the exotoxin SLS, encoded by a functional homologue of the nine-gene group A streptococcus sag operon. SLS expression contributes to the pathogenesis of streptococcal necrotising soft tissue infection.