Nature Communications paper on CRISPR-Cas

10/10/2016

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Researchers probe secrets of bacterial immune system

From a University of Otago press release:

Scientists from two Departments at the University of Otago and the Netherlands are continuing to unlock the secrets of a surprisingly flexible bacterial immune system, called CRISPR-Cas.

We infected the bacteria with plasmids not previously encountered, or with mutated plasmids triggering the primed adaptation response. By making use of the advances in next generation sequencing through New Zealand Genomics Ltd, we analysed more than 20 million newly acquired spacers." Associate Professor Fineran explains.

As part of the study Drs Brown and Biswas developed and used custom bioinformatic tools to analyse and interpret this type of high-throughput data, building on recently published tools and analysis (e.g. Biswas et al BMC Genomics, May 2016)

Just like humans, bacteria are constantly under attack by viruses that try to infect them by injecting viral DNA. This foreign DNA (together with other invading DNA, such as plasmids) has a major impact on the evolution of microorganisms. For example, the spread of antibiotic resistance and virulence factors are often introduced via invasion by foreign DNA.

CRISPR-Cas systems can remember and destroy invading DNA by storing short, invader-derived, pieces of DNA (called 'spacers') into their genetic memory banks. In an earlier study, the team discovered that viruses and plasmids, which can avoid recognition by mutating their DNA, will trigger the bacteria's CRISPR-Cas system to respond by quickly acquiring new immunological memories from these mutated threats. This process is called 'primed adaptation'.

 In their latest study, which appears this week in the prestigious journal Nature Communications, the team sought to understand how these new memories were selected during the primed adaptation response.

The team discovered that the acquisition of memories from plasmids not previously encountered was very inefficient in comparison to the mutated plasmids. By studying the order in which these new memories were acquired, the researchers developed a new model for primed adaptation.

Read the paper at Nature