C-di-AMP signaling in S. aureus

摘要 金黄色葡萄球菌是人类发病率和死亡率的主要原因，可引起 流行性感冒与囊性肺炎患者的皮肤软组织、术后创面及肺部感染 纤维化症患者。广泛的多重耐药使金黄色葡萄球菌被根除 越来越具有挑战性，需要更深入地了解生理学和 病原学与这些生物体有关的致病机制细菌生存和适应的一个关键方面 改变环境条件的能力是通过第二秒迅速改变细胞行为的能力 信使信号转导。C-di-AMP最近成为细菌的一种关键调节因子 生理、发病机制和免疫激活。在金黄色葡萄球菌的情况下，我们认为c- 金黄色葡萄球菌产生的Di-AMP有三个重要作用：(I)作为一种信号分子 金黄色葡萄球菌的代谢和抗生素耐药性，(Ii)作为一种细菌PAMP促进 病理性炎症和宿主对细菌感染的易感性，以及(Iii)作为 改变混合感染结果的细菌间信号。这些研究的发现可能 在金黄色葡萄球菌感染期间对抗生素治疗过程有重大影响，并可能 发现一个新的靶点来根除顽固的金黄色葡萄球菌及其引发的炎症。

Abstract Staphylococcus aureus is a leading cause of human morbidity and mortality, causing infection of the skin and soft tissues, post-surgical wounds, and lung infection among influenza and cystic fibrosis patients. Widespread multi-drug resistance has made eradication of S. aureus increasingly challenging, necessitating a deeper understanding of the physiology and pathogenesis associated with these organisms. A key aspect of bacterial survival and adaptation to altered environmental conditions is the ability to rapidly alter cellular behavior through second messenger signal transduction. C-di-AMP has recently emerged as a key regulator of bacterial physiology, pathogenesis, and immune activation. In the context of S. aureus, we believe that c- di-AMP produced by S. aureus has three important roles; (i) as a signaling molecule that mediates S. aureus metabolism and antibiotic resistance, (ii) as a bacterial PAMP that promotes pathological inflammation and host susceptibility to bacterial infection, and (iii) as a mediator of inter-bacterial signaling that alters the outcome of co-infections. Findings from these studies may have significant impacts on the course of antibiotic therapy during S. aureus infection and may uncover a novel target to eradicate recalcitrant S. aureus and the inflammation itpromotes.