Virulence control in group A Streptococcus by a two-component gene regulatory system:: Global expression profiling and in vivo infection modeling
Virulence control in group A Streptococcus by a two-component gene regulatory system:: Global expression profiling and in vivo infection modeling
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DOI：
10.1073/pnas.202353699
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发表时间：
2002-10-15
影响因子：
11.1
通讯作者：
Musser, JM
中科院分区：
文献类型：
--
作者：
Graham, MR;Smoot, LM;Musser, JM
由膜结合传感器和细胞质反应调节子组成的双组分基因调控系统是细菌感知和响应环境刺激的重要机制。A组链球菌是轻度感染和危及生命的侵袭性疾病的病原体，它产生许多毒力因子，促进人类的生存。一个名为CovRS(cov，毒力控制；csrRS)的双组分调控系统负向控制五个已证实或可能的毒力因子(衣壳、半胱氨酸蛋白酶、链激酶、链溶菌素S和链球菌酶)的表达。CovRs的失活导致侵袭性疾病小鼠模型的毒力增强。利用DNA微阵列和定量RT-PCR，我们发现COVR影响了15%(n=271)所有染色体基因的转录，包括许多编码介导宿主-病原体相互作用的表面蛋白和分泌蛋白的基因。COVR还通过影响转录调控基因的表达在基因调控网络中发挥核心作用，包括其他双组分系统。在小鼠软组织感染中也发现了受COVR影响的基因的差异转录。这一分析提供了一个重要的人类病原体的毒力基因网络的基因组规模的概述，并增加了对A组链球菌与宿主相互作用、促进生存和导致疾病的分子机制的洞察。
Two-component gene regulatory systems composed of a membrane-bound sensor and cytoplasmic response regulator are important mechanisms used by bacteria to sense and respond to environmental stimuli. Group A Streptococcus, the causative agent of mild infections and life-threatening invasive diseases, produces many virulence factors that promote survival in humans. A two-component regulatory system, designated covRS (cov, control of virulence; csrRS), negatively controls expression of five proven or putative virulence factors (capsule, cysteine protease, streptokinase, streptolysin S, and streptodomase). Inactivation of covRS results in enhanced virulence in mouse models of invasive disease. Using DNA microarrays and quantitative RT-PCR, we found that CovR influences transcription of 15% (n = 271) of all chromosomal genes, including many that encode surface and secreted proteins mediating host-pathogen interactions. CovR also plays a central role in gene regulatory networks by influencing expression of genes encoding transcriptional regulators, including other two-component systems. Differential transcription of genes influenced by covR also was identified in mouse soft-tissue infection. This analysis provides a genome-scale overview of a virulence gene network in an important human pathogen and adds insight into the molecular mechanisms used by group A Streptococcus to interact with the host, promote survival, and cause disease.