Oxidative stress elicited by phage infection induces Staphylococcal type III-A CRISPR-Cas system.

Abstract

In prokaryotes, the CRISPR-Cas system provides immunity to invading mobile genetic elements, but its expression is commonly repressed in the absence of phage infection to prevent autoimmunity. How bacteria senses phage infection and activates CRISPR-Cas system are poorly understood. Here, we demonstrate that an essential promoter Pcas, located within the cas1 gene, is the primary promoter driving expression of cas genes encoding the Cas10-Csm interference complex in Staphylococcus aureus type III-A CRISPR-Cas system during phage infection. As a conserved promoter in Staphylococci type III-A CRISPR-Cas system, the Pcas loses its ability to activate cas genes expression when mutated at the C186 site. Importantly, we find that the transcriptional regulator MgrA directly represses type III-A CRISPR-Cas system by interacting with Pcas to prevent autoimmunity. Upon phage infection, MgrA senses oxidative stress and dissociates from the Pcas, alleviating the transcriptional repression and subsequently triggering a robust immunity against phages. Our work provides evidence for the requirement of Pcas within cas1 during type III-A CRISPR-Cas interference stage, and reveals that MgrA-mediated regulation provides an effective mechanism for bacteria to balance avoiding autoimmunityand defending against phages.