Protection against Foreign DNA

Abstract

This chapter briefly addresses the well-characterized restriction-modification system (R-M), non-sugar-specific nucleases (SNSN), and histone-like nucleoid structuring (H-NS). It more specifically elaborates on clustered regularly interspaced short palindromic repeats (CRISPR). CRISPR/CRISPR-associated (Cas), a recently described microbial system, provides acquired immunity against phages and plasmids by targeting nucleic acids in a sequence-specific manner. CRISPR features may be exploited for typing purposes, ecological and epidemiological studies, and also for enhancing phage resistance in bacteria. R-M systems commonly act as the first line of intracellular defense against foreign DNA. Some SNSN, such as Vvn from Vibrio vulnificus and EndoI from Escherichia coli, are periplasmic and thus prevent the uptake of foreign DNA. The ubiquitous and predatory nature of phages may explain the overwhelming representation of phage sequences in CRISPR spacers, but a recent report showed that CRISPR can dramatically impact the ability of plasmids to transfer genetic material in Staphylococcus epidermidis. Also, this study experimentally confirmed that CRISPR targets DNA directly in Staphylococcus. The CRISPR RNAs (crRNAs) seem to specifically guide the Cas defense apparatus toward foreign nucleic acid molecules that match the sequence of the spacers. This study also showed that Cas3, a predicted HD nuclease fused to a DEAD-box helicase, is required for the phage-resistance phenotype. The extent of the impact of CRISPR on phage genomes is perhaps best illustrated by extensive genome recombination events observed in environmental phage populations in response to CRISPR.