Center for Molecular and Translational Human Infectious Diseases Research, The Methodist Hospital Research Institute, Houston, TX 77030, USA.
Microbiology (Reading). 2010 May;156(Pt 5):1342-1350. doi: 10.1099/mic.0.036558-0. Epub 2010 Jan 28.
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.
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进行分泌。虽然最初认为它在所有细菌中都是必不可少的，但最近的数据表明，SRP 在至少一些链球菌物种中是可有可无的。来自人类病原体 A 组链球菌 (GAS，化脓性链球菌) 的 SRP 预计由蛋白 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，我们报告说，编码 4.5S RNA 的基因发生突变，导致的表型与 ffh 突变观察到的表型既相似又不同。相似之处包括溶血素streptolysin O 的分泌减少，以及通过小鼠软组织感染模型评估的毒力减弱。差异包括编码 streptolysin O 和 NAD-糖基水解酶的基因的转录水平降低，以及 SpeB 蛋白酶的分泌减少。在亲本菌株和突变菌株之间观察到的几种转录丰度差异被证明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体外模型，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有助于 GAS 生长和持续存在的观点一致。最后，我们确定 4.5S RNA 对于 GAS 在感染的小鼠菌血症模型中引起致命感染是必不可少的。所提供的数据扩展了我们对 SRP 对重要革兰氏阳性病原体毒力的贡献的认识。
