Analysis of the role of CovR and CovS in the dissemination of Streptococcus pyogenes in invasive skin disease
Analysis of the role of CovR and CovS in the dissemination of Streptococcus pyogenes in invasive skin disease
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DOI：
10.1016/j.micpath.2006.01.005
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发表时间：
2006-05-01
影响因子：
3.8
通讯作者：
Scott, June R.
中科院分区：
文献类型：
--
作者：
Dalton, Tracy L.;Hobb, Rhonda I.;Scott, June R.
全局调控双组分系统CovR/S控制约15%的化脓性链球菌（A组链球菌; GAS）基因组的表达。最近，我们发现CovS在这种严格的人类病原体的一般应激反应中起着关键作用。因此，我们预期CovS和CovR都可能影响毒力。在这项工作中，小鼠皮下接种等基因非极性covR和covS缺失-取代突变体和等基因野生型菌株。CovS突变体在导致的病变外观和导致死亡的侵袭性疾病方面表现得像野生型亲本菌株。这与先前的结果一致，表明其同源传感器激酶的缺失不影响CovR磷酸化并导致其调节子阻遏的能力。然而，两种不同的covR缺失-取代突变体在小鼠中引起的侵袭性疾病和死亡显著低于野生型亲本菌株，尽管covR突变体产生的局部病变比野生型GAS菌株产生的病变更严重和化脓。因此，似乎CovR的产生增加了S.化脓性链球菌在该小鼠模型中引起严重的侵袭性疾病，因此是该生物体的重要毒力因子。(c)2006爱思唯尔有限公司保留所有权利。
The global regulatory two-component system CovR/S controls expression of about 15% of the Streptococcus pyogenes (group A streptococcus; GAS) genome. Recently, we found that CovS plays a pivotal role in general stress response of this strictly human pathogen. Therefore, we expected that both CovS and CovR might affect virulence. In this work, mice were inoculated subcutaneously with isogenic nonpolar covR and covS deletion-substitution mutants and the isogenic wild-type strain. The CovS mutant behaved like the wild-type parental strain in terms of resulting lesion appearance and invasive disease leading to death. This is in agreement with previous results suggesting that the absence of its cognate sensor kinase does not affect the ability of CovR to become phosphorylated and cause repression of its regulon. However, two different covR deletion-substitution mutants caused significantly less invasive disease and death in the mice than the wild-type parental strain, although the local lesions produced by the covR mutants were more severe and purulent than those resulting from the wild-type GAS strain. Thus, it appears that production of CovR increases the ability of S. pyogenes to cause severe invasive disease in this mouse model and therefore is an important virulence factor for this organism. (c) 2006 Elsevier Ltd. All rights reserved.