You may have heard about clustered regularly interspaced short palindromic repeats, or CRISPR, as a revolutionary gene-editing tool. However, CRISPR was initially discovered as an immune defence system that bacteria use to fight off viruses. These viruses, known as bacteriophages (a term coined 100 years ago by Canadian-born microbiologist Félix d’Hérelle that means ‘bacteria-eaters’) inject their DNA into a bacterial cell and use the bacterium’s machinery to make copies of themselves before bursting out of the cell. Bacteria with CRISPR systems, when infected, can copy short sequences of viral DNA and store it in their own genome. Interestingly, these viral DNA sequence fragments are stored in ordered arrays in the bacterial genome, creating a chronological record of past infections. This remarkable form of bacterial immune ‘memory’ is useful to defend against future infections. If the bacterium or its offspring are attacked by the same bacteriophage again, they can use the stored viral DNA sequence to recognise and degrade the viral DNA to stop the infection.
Despite the rapid growth of CRISPR research, the way that bacteria acquire short viral DNA sequences remains poorly understood. In a recent study, Hynes et al. examined this process in greater depth. They found that bacteria are more likely to acquire viral DNA (and immunity) when infected by defective bacteriophages. These viruses can enter bacteria but fail to replicate and kill the host. This provides an excellent opportunity for the bacteria to acquire and store the DNA from the defective bacteriophage in their CRISPR system. Importantly, these bacteria that were ‘vaccinated’ by infection with a defective phage were immune to future infections by intact normal phage. This is similar to how some vaccines work, whereby exposure to attenuated pathogens trains our immune system to recognize and combat the real thing.
The study of bacteriophage has led to the discovery of research and biotech tools like restriction enzymes and DNA ligase, that allow us to cut and glue DNA pieces together, and CRISPR, which enables more specific gene editing. CRISPR has many promising applications in health and biotechnology. Better understanding the molecular mechanisms of CRISPR systems can help us improve existing technologies and discover new ones.
Summary written by: Clara Fikry
To read the full article, please click the following link:
Adaptation in bacterial CRISPR-Cas immunity can be driven by defective phages
Alexander P. Hynes, Manuela Villion, Sylvain Moineau
Note from the PLoSibilities editors: Two authors of this Nature Communications paper, Drs. Sylvain Moineau (Université Laval) and Alexander Hynes (McMaster University) will be attending CSV2018: The 2nd Symposium of the Canadian Society for Virology, in Halifax, Nova Scotia on June 13-15, 2018. To learn more about this symposium, go to: https://www.fourwav.es/view/589/info/
