Quorum Sensing Inhibits Type III-A CRISPR-Cas System Activity Through Repressing Positive Regulators SarA and ArcR in Staphylococcus Aureus

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 have been extensively studied, but the regulation of this system in Staphylococci remains unclear. Here, it is shown that the cell-cell communication, known as quorum sensing (QS), inhibits the expression and activity of the type III-A CRISPR-Cas system in S. aureus. The QS regulator, AgrA, directly binds to the promoters of two transcriptional regulators encoding the genes sarA and arcR to inhibit their expression. However, both SarA and ArcR act as positive regulators that promote the transcription of cas genes by directly binding to a novel promoter Pcas. Furthermore, the Pcas of 300 bp located in cas1 displays as a critical regulatory node to initiate the transcription of cas10 and csm3. Our data reveal 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.