The 4.5S RNA component of the signal recognition particle is required for group A Streptococcus virulence.
The 4.5S RNA component of the signal recognition particle is required for group A Streptococcus virulence.
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DOI：
10.1099/mic.0.036558-0
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发表时间：
2010-05
期刊：
影响因子：
1.5
通讯作者：
J. Treviño;N. Pérez;P. Sumby
中科院分区：
文献类型：
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作者：
J. Treviño;N. Pérez;P. Sumby
信号识别颗粒（SRP）是一种核糖核蛋白复合物，以共翻译的方式靶向蛋白质分泌。虽然最初认为在所有细菌中都是必需的，但最近的数据显示，SRP至少在某些链球菌物种中是必需的。预测来自人类病原体A组链球菌（GAS，化脓性链球菌）的SRP由蛋白Ffh和4.5S RNA组成。ffh的缺失改变了几种GAS蛋白的分泌，并导致毒力严重降低。在这里，我们报告，编码4.5S RNA的基因突变导致表型相似和不同的观察后ffh突变。相似之处包括溶血素链球菌溶血素O的分泌减少，以及通过鼠软组织感染模型评估的毒力减弱。差异包括编码链球菌溶血素O和NAD-糖水解酶的基因的转录水平降低，以及SpeB蛋白酶的分泌减少。亲本和突变株之间的转录丰度的几个差异被证明是依赖于传感器激酶编码基因covS。使用人唾液中的生长作为上呼吸道感染的离体模型，我们发现4.5S RNA突变导致菌落形成单位随时间减少10倍，这与4.5S RNA在上呼吸道感染期间促进GAS生长和持久性一致。最后，我们确定了4.5S RNA是GAS在小鼠菌血症感染模型中引起致死性感染所必需的。提出的数据扩展了我们的知识的贡献SRP的一个重要的革兰氏阳性病原体的毒力。
The signal recognition particle (SRP) is a ribonucleoprotein complex that targets proteins for secretion in a co-translational manner. While originally thought to be essential in all bacteria, recent data show that the SRP is dispensable in at least some streptococcal species. The SRP from the human pathogen group A Streptococcus (GAS, Streptococcus pyogenes) is predicted to be composed of protein Ffh and 4.5S RNA. Deletion of ffh alters the secretion of several GAS proteins, and leads to a severe reduction in virulence. Here, we report that mutation of the gene encoding 4.5S RNA results in phenotypes both similar to and distinct from that observed following ffh mutation. Similarities include a reduction in secretion of the haemolysin streptolysin O, and attenuation of virulence as assessed by a murine soft tissue infection model. Differences include a reduction in transcript levels for the genes encoding streptolysin O and NAD-glycohydrolase, and the reduced secretion of the SpeB protease. Several differences in transcript abundance between the parental and mutant strain were shown to be dependent on the sensor-kinase-encoding gene covS. Using growth in human saliva as an ex vivo model of upper respiratory tract infection we identified that 4.5S RNA mutation leads to a 10-fold reduction in colony-forming units over time, consistent with the 4.5S RNA contributing to GAS growth and persistence during upper respiratory tract infections. Finally, we determined that the 4.5S RNA was essential for GAS to cause lethal infections in a murine bacteraemia model of infection. The data presented extend our knowledge of the contribution of the SRP to the virulence of an important Gram-positive pathogen.