Role of streptolysin O in a mouse model of invasive group A streptococcal disease

Role of streptolysin O in a mouse model of invasive group A streptococcal disease
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DOI:
10.1128/iai.68.11.6384-6390.2000
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发表时间:
2000-11-01
影响因子:
3.1
通讯作者:
Scott, JR
Scott, JR
中科院分区:
医学2区
文献类型:
--
作者:
Limbago, B;Penumalli, V;Scott, JR

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A组链球菌(GAS)的许多毒力因子并不是在所有临床分离株中表达。其中一个公认的毒力因子是链球菌溶血素O(Slo),这是一种对许多enrichment细胞类型具有良好特征的细胞溶解活性的蛋白质。在其他细菌病原体中,与Slo同源的蛋白质已被证明是毒力所必需的,但Slo在CAS中的作用以前没有被研究过。为了研究Slo在GAS毒力中的作用,我们在侵袭性疾病的小鼠模型中检测了可逆和稳定的突变体。当使用可回复突变株感染小鼠时,从感染动物伤口和脾脏中分离的细菌的回复频率是接种物的100倍以上,表明动物中存在对Slo(+)GAS的选择压力。用稳定的突变体Slo进行的实验表明,Slo不是形成坏死性病变所必需的,也不是从病变中逃逸引起播散性感染所必需的。在感染稳定突变体Slo后存活的小鼠中,50%的脾脏中存在细菌,表明Slo(-)GAS的传播并不总是引起疾病。最后,与感染野生型GAS的小鼠相比,感染稳定突变体Slo的小鼠的死亡率显著降低(P < 0.05),表明Slo在GAS毒力中起重要作用。
Many of the virulence factors that have been characterized for group A streptococci (GAS) are not expressed in all clinical isolates. One putative virulence factor that is present among most is streptolysin O (Slo), a protein with well-characterized cytolytic activity for many enkaryotic cells types. In other bacterial pathogens, proteins homologous to Slo have been shown to be essential for virulence, but the role of Slo in CAS had not been previously examined. To investigate the role of Slo in GAS virulence, we examined both revertible and stable slo mutants in a mouse model of invasive disease. When the revertible slo mutant was used to infect mice, the reversion frequency of bacteria isolated from the wounds and spleens of infected animals was more than 100 times that of the inoculum, indicating that there was selective pressure in the animal for Slo(+) GAS. Experiments with the stable slo mutant demonstrated that Slo was not necessary for the formation of necrotic lesions, nor was it necessary for escape from the lesion to cause disseminated infection. Bacteria were present in the spleens of 50% of the mice that survived infection with the stable slo mutant, indicating that dissemination of Slo(-) GAS does not always cause disease. Finally, mice infected with the stable slo mutant exhibited a significant decrease in mortality rates compared to mice infected with wild-type GAS (P < 0.05), indicating that Slo plays an important role in GAS virulence.