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Hereditary immunity in bacteria: the CRISPR/Cas system

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  • Biology

Abstract

Bacteriophages, or phages, are parasites that are a constant threat to bacteria. Outnumbered by a factor ten, bacteria have developed a number of strategies to avoid phage infection. Such phage infection proceeds by five major events. Bacterial resistance mechanisms interfere on several of these events. By altering extracellular matrix components bacteria avoid phage recognition and adsorption. The penetration of phage genomic material can be avoided by Superinfection-Exclusion systems. Restriction – Modification systems degrade foreign DNA, thereby preventing transcription. A range of Abortive infection systems cause host suicide before phage synthesis has completed. A recently discovered system of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) is suggested to provide specific and adaptive phage resistance. At the first encounter with a bacteriophage a short sequence, a CRSIPR, is obtained and stored in the CRISPR for future protection, somewhat similar to a immune system. When the same phage is encountered again later, the CRISPR sequence is used to recognize and degrade the invading phage DNA. CRISPR associated (Cas) genes are separated in core genes and subtype specific genes. The translated proteins are essential for both acquisition of new spacers as well for CRISPR mediated defense. Although a lot of data has been published in a relative short period, the underlying mechanisms are to be unraveled. There are, however, strong indications and suggestions for Cas protein functions like nuclease, integrase, helicase and polymerase. A major part of CRISPR research is conducted in Streptococcus thermophilus, Escherichia coli and bacterial species that harbor an Ecoli subtype CRISPR locus. This thesis focuses on these studies.

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