# LysR-type regulator LrhA promotes CRISPR-Cas immunity in Escherichia coli

## TL;DR

A new regulator called LrhA helps control CRISPR-Cas immunity in E. coli by adjusting gene activity to fight viruses and plasmids.

## Contribution

LrhA is identified as a novel CRISPR-Cas activator that modulates adaptive immunity through differential regulation of cas gene transcription.

## Key findings

- LrhA enhances CRISPR-Cas immunity by promoting cas gene transcription in high-expression strains.
- Moderate LrhA activity accelerates plasmid clearance through enhanced spacer acquisition.
- Optimal adaptive immunity is achieved with intermediate cas gene transcription via positive feedback.

## Abstract

The CRISPR-Cas defense system safeguards prokaryotes against foreign genetic elements. Its activity is determined by the combined effects of adaptation and interference. However, the dynamic regulation of these two processes remains not fully understood. In this study, we identify the LysR-type transcriptional regulator LrhA, which is differentially expressed in various Escherichia coli strains, as a novel CRISPR-Cas activator that plays a critical role in modulating host defense levels. In a representative strain expressing a high level of LrhA, the regulator enhances CRISPR-Cas-mediated adaptive immunity against bacteriophage infection by promoting cas gene transcription through direct interaction with the promoter of the cas operon. Moderate activation of cas genes by weakly expressed LrhA in another representative strain efficiently accelerates the clearance of horizontally transferred CRISPR-targeted plasmids by enhancing spacer acquisition via interference-driven adaptation. This divergence, likely a result of genome evolution, suggests that adaptive immunity is optimized with intermediate transcription levels of cas genes by triggering positive feedback between adaptation and interference. Collectively, our findings highlight the crucial role of LrhA in fine-tuning host defense responses.

Graphical Abstract