LrhA promotes CRISPR-Cas immunity by promoting reciprocal interplay between interference and primed adaptation in Escherichia coli

The CRISPR-based defense system protects prokaryotes against invading plasmids and viruses by memorizing their nucleotide-sequence traits (adaptation) and destructing the nucleic acids (interference). Previous studies have indicated that CRISPR-Cas adaptive immunity is the outcome of the combined effect of adaptation and interference, but the environmental and physiological cues that coordinate these two processes are unclear. Here, we identify the LysR-type transcriptional regulator LrhA as an important CRISPR-Cas regulator, which promotes the clearance of CRISPR-targeted plasmid more efficiently at 37 ℃ than at 30 ℃ in Escherichia coli , by increasing the acquisition of new spacers via interference-driven adaptation. LrhA directly binds to the promoter of the cas operon to activate the transcription of cas genes required for adaptation and interference, thereby enhancing the CRISPR-Cas adaptive immunity. Altogether, our results demonstrate that LrhA plays a pivotal role in coordinating CRISPR adaptation and interference at the body temperature in a gut-dwelling bacterium. ### Competing Interest Statement The authors have declared no competing interest.