Department of Microbiology and Molecular Medicine, CMU, Medical Faculty, University of Geneva, Genève, Switzerland.
RNA Biol. 2013 Jan;10(1):157-65. doi: 10.4161/rna.22899. Epub 2012 Dec 10.
DEAD-box RNA helicases are present in almost all living organisms and participate in various processes of RNA metabolism. Bacterial proteins of this large family were shown to be required for translation initiation, ribosome biogenesis and RNA decay. The latter is primordial for rapid adaptation to changing environmental conditions. In particular, the RhlB RNA helicase from E. coli was shown to assist the bacterial degradosome machinery. Recently, the CshA DEAD-box proteins from Bacillus subtilis and Staphylococcus aureus were shown to interact with proteins that are believed to form the degradosome. S. aureus can cause life-threatening disease, with particular concern focusing on biofilm formation on catheters and prosthetic devices, since in this form the bacteria are almost impossible to eradicate both by the immune system and antibiotic treatment. This persistent state relies on the expression of surface encoded proteins that allow attachment to various surfaces, and contrasts with the dispersal mode of growth that relies on the secretion of proteins such as hemolysins and proteases. The switch between these two states is mainly mediated by the Staphylococcal cell density sensing system encoded by agr. We show that inactivation of the cshA DEAD-box gene results in dysregulation of biofilm formation and hemolysis through modulation of agr mRNA stability. Importantly, inactivation of the agrA gene in the cshA mutant background reverses the defect, indicating that cshA is genetically upstream of agr and that a delicate balance of agr mRNA abundance mediated through stability control by CshA is critical for proper expression of virulence factors.
DEAD-box RNA 解旋酶几乎存在于所有生物中，参与 RNA 代谢的各种过程。该大家族的细菌蛋白被证明是翻译起始、核糖体生物发生和 RNA 降解所必需的。后者对于快速适应不断变化的环境条件至关重要。特别是，大肠杆菌的 RhlB RNA 解旋酶被证明有助于细菌降解体机制。最近，枯草芽孢杆菌和金黄色葡萄球菌的 CshA DEAD-box 蛋白被证明与被认为形成降解体的蛋白质相互作用。金黄色葡萄球菌可引起危及生命的疾病，特别关注导管和假体设备上生物膜的形成，因为在这种形式下，细菌几乎不可能被免疫系统和抗生素治疗同时消除。这种持续状态依赖于表达表面编码蛋白，使细菌能够附着在各种表面上，这与依赖于分泌溶血性蛋白和蛋白酶等蛋白的分散生长模式形成对比。这两种状态之间的转换主要由 agr 编码的金黄色葡萄球菌细胞密度感应系统介导。我们表明，通过调节 agr mRNA 稳定性，cshA DEAD-box 基因的失活导致生物膜形成和溶血失调。重要的是，在 cshA 突变背景下 agrA 基因的失活逆转了缺陷，表明 cshA 在遗传上位于 agr 之前，并且通过 CshA 对 agr mRNA 丰度的稳定性控制介导的微妙平衡对于适当表达毒力因子至关重要。
