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: Microbes utilize defence systems with fundamental similarities to our innate and adaptive immune responses to protect themselves from harmful invaders. One system, made up of CRISPR loci & Cas proteins, incorporates recognizable features from the genomes of viruses (bacteriophages) and plasmids into bacterial genomes, where they are later used to direct a ribonucleoprotein complex to destroy invading nucleic acids upon re-exposure. CRISPR-mediated defence against invasive nucleic acids is found in most archaea and many eubacteria. Many aspects of this newly described defence system have not been worked out, including the molecular mechanisms by which foreign nucleic acids are incorporated into microbial genomes during adaption and destroyed during interference. In this issue of Molecular Microbiology, DeLisa and colleagues provide insight into how this form of microbial immunity might be regulated in eubacteria. They demonstrate that Escherichia coli CRISPR-mediated immunity requires the presence of the BaeSR two-component system under certain conditions. Since BaeSR regulate an envelope stress response, their data imply that immunity against invading, foreign nucleic acids may be somehow linked to stresses to the bacterial membrane. These observations will help pave the way to understanding how and when CRISPR-based immunity may be important in driving evolution and adaptation in eubacteria.

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