Humar Deepali, Datta Vivekananda, Bast Darrin J, Beall Bernard, De Azavedo Joyce C S, Nizet Victor
Department of Medicine, Division of Infectious Diseases, University of California, San Diego 92093, USA.
Lancet. 2002 Jan 12;359(9301):124-9. doi: 10.1016/S0140-6736(02)07371-3.
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.
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.
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.
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.
我们遇到了3例由β溶血性G群链球菌引起的严重坏死性软组织感染患者。由于与A群链球菌引起的侵袭性感染在临床上有很强的相似性，我们研究了共享的β溶血性表型与疾病发病机制之间的潜在联系。
采用杂交、DNA测序、靶向诱变和互补研究来确定G群链球菌β溶血活性的遗传基础。在小鼠中检测G群链球菌β溶血素在产生坏死性感染中的作用。
每位患者都有基础疾病。β溶血性G群链球菌是清创坏死组织中唯一分离出的微生物。G群链球菌染色体包含一个与编码β溶血素链球菌溶血素S（SLS）的9基因A群链球菌sag操纵子同源的基因。对G群链球菌中假定的SLS结构基因sagA进行靶向诱变消除了β溶血活性。皮下注射野生型A群链球菌或G群链球菌的小鼠出现了炎症病变，细菌计数高，有明显的中性粒细胞浸润，以及弥漫性组织坏死的组织病理学证据。在注射了同基因A群链球菌或G群链球菌SLS阴性突变体的小鼠中未发现这些变化。
在有基础疾病的患者中，β溶血性G群链球菌可引起类似于A群链球菌引起的坏死性软组织感染。G群链球菌的β溶血性表型由外毒素SLS产生，该毒素由9基因A群链球菌sag操纵子的功能同源物编码。SLS表达有助于链球菌坏死性软组织感染的发病机制。
