A recent collaborative study involving researchers from the Fineran Lab has uncovered how viruses fight back against the CRISPR-Cas bacterial adaptive immune systems.
The study, published in Nature Microbiology, uncovered a new arsenal of anti-CRISPR proteins produced by viruses that enable them to circumvent CRISPR-Cas adaptive immunity in their arms race with bacteria.
The project was led from the groups of Alan Davidson and Karen Maxwell from the University of Toronto. Collaborators from Associate Professor Peter Fineran’s group were Dr Raymond Staals, Corinda Taylor and Bridget Watson.
CRISPR-Cas systems are have been widely re-purposed as accurate gene editing tools, but their natural role is to provide bacteria with an adaptive immunity. Bacteria can be infected by phages, which are viruses that specifically infect bacteria, and by other invaders, such as plasmids that encode antibiotic resistance. CRISPR-Cas provides bacteria with a genetic immunological memory of past infections, giving resistance to these invaders.
Alan Davidson’s group discovered the phage-encoded anti-CRISPR proteins that inhibit a CRISPR-Cas system in the human pathogen Pseudomonas aeruginosa. Anti-CRISPRs give the phages the upper hand when trying to compete with CRISPR-Cas immunity, but it was not clear how widespread this phenomenon was.
In the current study new families of anti-CRISPRs were identified in diverse phages and plasmids and were shown to inhibit CRISPR-Cas systems in different bacteria. CRISPR-Cas systems come in many different varieties, and remarkably, one of the newly discovered anti-CRISPR proteins was dual specificity, inhibiting the activity of two types of CRISPR-Cas systems. The apparent widespread distribution of anti-CRISPRs suggest that phages and plasmids can evade bacterial immunity to allow their transfer between bacteria.
With the increase in antibiotic resistance, people are investigating the use of phages as bacteria-specific antimicrobials, but the development of CRISPR-Cas phage resistance is a concern. It may be possible to use phages with anti-CRISPRs to reduce the ability of resistance development.
In contrast, anti-CRISPR proteins might be contributing to the ability of plasmids to spread between bacteria by shutting down the bacterial immune system. This has implications for the spread of antibiotic resistance genes between bacteria.