C-di-AMP signaling in S. aureus

AbstractStaphylococcus aureus is a leading cause of human morbidity and mortality, causing infection ofthe skin and soft tissues, post-surgical wounds, and lung infection among influenza and cysticfibrosis patients. Widespread multi-drug resistance has made eradication of S. aureusincreasingly challenging, necessitating a deeper understanding of the physiology andpathogenesis associated with these organisms. A key aspect of bacterial survival and adaptationto altered environmental conditions is the ability to rapidly alter cellular behavior through secondmessenger signal transduction. C-di-AMP has recently emerged as a key regulator of bacterialphysiology, 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 mediatesS. aureus metabolism and antibiotic resistance, (ii) as a bacterial PAMP that promotespathological inflammation and host susceptibility to bacterial infection, and (iii) as a mediator ofinter-bacterial signaling that alters the outcome of co-infections. Findings from these studies mayhave significant impacts on the course of antibiotic therapy during S. aureus infection and mayuncover a novel target to eradicate recalcitrant S. aureus and the inflammation itpromotes.