Bacteriophages use Anti-CRISPR proteins (Acrs) to inhibit these immune systems, infecting the bacteria. Because of the prevalence of CRISPR-Cas systems in bacteria (about 40%) and archaea (90%) and ability of Acrs to act as “off-switches” for these systems, there is a push to further discover and characterize these proteins. CRISPR-Cas systems have extensive uses in gene editing and molecular diagnostic technologies. CRISPR-Cas Type III systems have a complementary off-switch (anticrispr) which provide a potential alternative to current CRISPR-Cas systems in development for therapeutic applications, particularly for combating the increasing antibiotic resistance in bacterial infections. 

Anti-CRISPR protein (AcrIIIA1) specifically inactivates the Type III-A CRISPR-Cas system. It works by binding the components of the CRISPR system and blocking the function of the system. AcrIIIA1 is also toxic to bacteria as it binds and cleaves critical components of the bacterial translation apparatus. Due to these traits, AcrIIIA1 may be useful in (1) selectively turning off CRISPR activity during gene editing to reduce off-target effects; (2) overcoming bacterial CRISPR-Cas immunity, increasing the effectiveness of whole phage therapeutics; and (3) acting as an antimicrobacterial. 

Benefits

AcrIIIA1 disrupts translation machinery in Staphylococcus. AcrIIIA1 functions to switch-off the CRISPR-Cas Type III systems (the bacterial immune system).

Application

Whole-phage therapeutics, gene editing, antimicrobial

Publication

Lucy Chou-Zheng, Olivia Howell, Tori A Boyle, Motaher Hossain, Forrest C Walker, Emma K Sheriff, Barbaros Aslan, Asma Hatoum-Aslan, AcrIIIA1 is a protein–RNA anti-CRISPR complex that targets core Cas and accessory nucleases, Nucleic Acids Research, Volume 52, Issue 22, 11 December 2024, Pages 13490–13514, https://doi.org/10.1093/nar/gkae1006 [2]