Dissecting conserved molecular mechanisms of biological toxin activity through CRISPR screening

Toxins, substances that are produced by living organisms with the potential to cause harm, demonstrate great diversity in their structure, function, and origin. Though some toxins have been repurposed for use as novel therapeutics, research tools, or for application in agriculture, the mechanism of action for many toxins remains uncharacterised. Pooled CRISPR screens offer a high-throughput and unbiased method for rapid annotation of the host cell genome and identification of factors mediating or modifying intoxication. In this review, we provide a brief overview of CRISPR screening before detailing how screens have been used to characterise toxins from various biological kingdoms. We highlight certain cell entry factors and intracellular processes as conserved targets of various toxins. Finally, we highlight limitations in the methods of CRISPR screens used thus far and make recommendations as to how screen design can be modified to more completely characterise toxin activity and elucidate systemic effects of intoxication.