The role of CRISPR/cas system in the development of bacteriophage resistance

Abstract

Acquisition of foreign DNA can be of advantage or disadvantage to the host cell. New DNAs can increase the fitness of an organism to certain environmental conditions or on the other hand, replication and maintenance of incorporated nucleotide sequences can be a burden for the host cell. These circumstances have resulted in development of certain cellular mechanisms limiting horizontal gene transfer, including the immune system of vertebrates or RNAi mechanisms in Eukaryotes. Also in Prokaryotes specific systems have been characterized, which are aimed especially at limiting invasion of bacteriophage DNA, e.g. adsorption inhibition, injection blocking, restriction/modification, abortive infection. Quite recently, another distinct mechanism limiting horizontal transfer of genetic elements has been identified in Prokaryotes and shown to protect microbial cells against exogenous nucleic acids of phage or plasmid origin. This system has been termed CRISPR/cas and consists of two main components: (i) the CRISPR (clustered, regularly interspaced short palindromic regions) locus and (ii) cas genes, encoding CRISPR-associated (Cas) proteins. In simplest words, the mechanism of CRISPR/cas activity is based on active integration of small fragments (proto-spacers) of the invading DNAs (phage or plasmids) into microbial genomes, which are subsequently transcribed into short RNAs that direct degradation of foreign invading DNA elements. By this way, the host organism acquires immunity toward mobile elements carrying matching sequences. The CRISPR/cas system is regarded as one of the earliest defense system that has evolved in prokaryotic organisms. It is inheritable, but at the same time unstable when regarding the evolutionary scale. Comparative sequence analyses indicate that CRISPR/cas systems play an important role in the evolution of microbial genomes and their predators, bacteriophages.