RivR is a negative regulator of virulence factor expression in group A Streptococcus.
RivR is a negative regulator of virulence factor expression in group A Streptococcus.
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RivR 是 A 组链球菌毒力因子表达的负调节因子。
DOI：
10.1128/iai.00703-12
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发表时间：
2013
影响因子：
3.1
通讯作者：
Sumby,Paul
中科院分区：
文献类型：
--
作者：
Trevino,Jeanette;Liu,Zhuyun;Cao,TramN;Ramirez-Pena,Esmeralda;Sumby,Paul
细菌病原体A群链球菌（GAS）引起人类疾病，范围从自限性咽炎（也称为链球菌性咽喉炎）到严重侵袭性坏死性筋膜炎（也称为食肉综合征）。为了控制毒力因子的表达，GAS利用基于蛋白质和rna的调控机制。在这里，我们报道转录因子RivR （rofa样蛋白IV）负调控编码透明质酸胶囊生物合成蛋白（hasABC； ~ 7倍）和蛋白g相关α2-巨球蛋白结合蛋白（grab； ~ 29倍）的mrna的丰度。我们的数据与之前对RivR规则的研究有很大不同。鉴于grabandhasabcare也受到双组分系统CovR/S（控制毒力）的负调控，我们测试了RivR是否通过CovR/S起作用。对RivR和CovR单突变株和双突变株的比较表明，RivR需要CovR活性来调控grabandhasabr。对rivrmrna上游区域的分析发现了一个新的启动子，该启动子的缺失使rivrmrna丰度降低了70%。与亲本菌株和互补菌株相比，arivmutant对人角质形成细胞的粘附能力降低，这种表型在用透明质酸酶进行GAS预处理后被消除，这突出了RivR在定植过程中胶囊调节的重要性。该突变株在菌血症感染的小鼠模型中也被减弱了毒力。因此，我们确定RivR是GAS毒力的重要调节因子，并为控制该病原体毒力因子产生的调节网络提供了新的见解。
The bacterial pathogen group A Streptococcus (GAS) causes human diseases ranging from self-limiting pharyngitis (also known as strep throat) to severely invasive necrotizing fasciitis (also known as the flesh-eating syndrome). To control virulence factor expression, GAS utilizes both protein- and RNA-based mechanisms of regulation. Here we report that the transcription factor RivR (RofA-like protein IV) negatively regulates the abundance of mRNAs encoding the hyaluronic acid capsule biosynthesis proteins (hasABC; ∼7-fold) and the protein G-related α2-macroglobulin-binding protein (grab; ∼29-fold). Our data differ significantly from those of a previous study of the RivR regulon. Given thatgrabandhasABCare also negatively regulated by the two-component system CovR/S (controlofvirulence), we tested whether RivR functions through CovR/S. A comparison ofrivandcovsingle and double mutant strains showed that RivR requires CovR activity forgrabandhasABCregulation. Analysis of the upstream region ofrivRidentified a novel promoter the deletion of which reducedrivRmRNA abundance by 70%. ArivRmutant strain had a reduced ability to adhere to human keratinocytes relative to that of the parental and complemented strains, a phenotype that was abolished upon GAS pretreatment with hyaluronidase, highlighting the importance of capsule regulation by RivR during colonization. TherivRmutant strain was also attenuated for virulence in a murine model of bacteremia infection. Thus, we identify RivR as an important regulator of GAS virulence and provide new insight into the regulatory networks controlling virulence factor production in this pathogen.