Quorum sensing represses Type III-A CRISPR-Cas in Staphylococcus aureus by inhibiting SarA and ArcR-mediated activation of cas genes. Quorum sensing represses Type III-A CRISPR-Cas in Staphylococcus aureus by inhibiting SarA and ArcR-mediated activation of cas genes

CRISPR-Cas is an adaptive immune system that protects prokaryotes from the invasion of foreign genetic elements. The components and immunity mechanisms of CRISPR-Cas has been extensively studied, but the regulation of this system in Staphylococci remains unclear. Here, we show that the cell-cell communication, known as quorum sensing (QS) represses the expression and interference of Type III-A CRISPR-Cas system by preventing the SarA and ArcR-mediated activation of cas genes in S. aureus. The QS regulator, AgrA, directly binds the promoters of two transcriptional regulator encoding genes sarA and arcR to inhibit their expression. However, both SarA and ArcR act as positive regulators to promote the transcription of cas genes through direct binding a novel promoter Pcas, which was identified to locate within cas1 displays as a critical regulatory node to initiate the transcription of cas10 and csm3. Our results unveil a new regulatory mechanism for QS-mediated repression of the Type III-A CRISPR-Cas system, which may allow S. aureus to acquire foreign genetic elements encoding antibiotic resistance or virulence factors specifically at high cell density.