CRISPR-Cas Systems: A Review of their Role as Non-Canonical Antimicrobials to Combat Drug Resistance

Background: Since their discovery in 1928, antibiotics have revolutionized modern human medicine. A direct consequence of their widespread use and abuse is the concomitant development of sophisticated resistance mechanisms by microbes to most of these antibiotic agents. With a sharp fall in the number of new antibiotic agents under development, due to a decline in sectoral investment by the major pharmaceutical firms, now more than ever, there is an urgent need for alternative antimicrobial agents, to overcome the global health crisis of antimicrobial resistance. One such alternative are the CRISPR-Cas systems. In this review, we discuss the discovery and evolution of the CRSIPR-Cas system, their classification, their application as antimicrobial agents and the current limitations to their use.

Main Body: Since their discovery in 1987, the CRISPR-Cas systems have evolved to possess several applications in biomedical science, including their use in gene editing, genome engineering and for treating genetic diseases. One potential application that has received less attention however is their use as sequence-specific antimicrobials. The three steps in their mechanism of action – spacer acquisition, biogenesis and interference, have been demonstrated to be effective for the highly-specific elimination of targeted bacterial strains from a mixed population of bacteria in a microbial community, as well as for driving a positive selection pressure for the development of antibiotic-sensitive bacterial strains, even to the point of reversing antimicrobial resistance through the elimination of the resistance genes. However, the use of CRISPR-based antimicrobials is fraught with several challenges, ranging from concerns about delivery platforms (phage-based vs. conjugative plasmids), their application on complex microbial communities, safety considerations, to the possibility of resistance and the many regulatory hurdles against their widespread use.

Conclusion: While their efficacy has been confirmed, more studies are required to further establish CRISPR-Cas based antimicrobials in conventional medical practice.