Fried to a CRISPR

Abstract

Molecular Biology The CRISPR-Cas system, found in many bacteria and archea, is known as an adaptive defense against the invasion of foreign DNA. The bacteria/archea capture fragments of plasmids and phages and incorporate them into one or more CRIPSR loci. The captured sequences are then transcribed and cleaved into short CRISPR (cr)RNAs, which, when bound by a Cas nuclease complex, are used to target the invading nucleic acid for destruction. Previous work suggested a link between bacterial virulence and the CRISPR system. Sampson et al. now show that in the intracellular parasite Francisella novicida , CRISPR-Cas is required for evasion of the host's innate immune system. The F. novicida CRISPR locus encodes a small CRISPR/Cas-associated RNA (scaRNA) that has complementarity to both a trans-acting crRNA (tracrRNA) and its own lipoprotein gene. The scaRNA, together with the tracrRNA and Cas9 nuclease, acts to repress expression of the F. novicida lipoprotein during host infection. This allows the infecting bacteria to avoid detection by one of the host's pathogen pattern recognition receptors, which binds to bacterial lipoproteins, and activates the host's innate immune response. CRISPR-Cas regulation of endogenous genes may play a broad role in bacterial virulence. Nature 10.1038/nature12048 (2013).