Abstract
The emergence of antimicrobial-resistant (AMR) bacteria has become one of the most serious threats to global health, necessitating the development of novel antimicrobial strategies. CRISPR (clustered regularly interspaced short palindromic repeats)-Cas (CRISPR-associated) system, known as a bacterial adaptive immune system, can be repurposed to selectively target and destruct bacterial genomes other than invasive genetic elements. Thus, the CRISPR-Cas system offers an attractive option for the development of the next-generation antimicrobials to combat infectious diseases especially those caused by AMR pathogens. However, the application of CRISPR-Cas antimicrobials remains at a very preliminary stage and numerous obstacles await to be solved. In this mini-review, we summarize the development of using type I, type II, and type VI CRISPR-Cas antimicrobials to eradicate AMR pathogens and plasmids in the past a few years. We also discuss the most common challenges in applying CRISPR-Cas antimicrobials and potential solutions to overcome them.
Highlights
CRISPR-Cas system has been identified as an adaptive immune system which enables prokaryotes to resist invading genetic elements through foreign DNA/RNA destruction (Marraffini, 2015)
Owing to the power of RNA-guided destruction of nucleic acids, CRISPR-Cas system becomes a promising candidate for the development of the next-generation antimicrobials to deal with infectious diseases especially those caused by AMR pathogens (Figure 2A)
Type I CRISPR-Cas systems, recognized by the signature Cas3 nuclease, are the predominant systems found in prokaryotes which account for nearly 60% of all CRISPR-Cas systems identified so far (Makarova et al, 2015)
Summary
CRISPR-Cas system has been identified as an adaptive immune system which enables prokaryotes to resist invading genetic elements (basically viruses and plasmids) through foreign DNA/RNA destruction (Marraffini, 2015). Increasing studies have shown that CRISPR-Cas systems are emerging as one of the most promising candidates to deal with antimicrobial resistance in recent years (Bikard and Barrangou, 2017; Gholizadeh et al, 2020) In this mini-review, we summarize the recent advances in developing CRISPR-Cas antimicrobials and discuss the main challenges in practical uses as well as their potential solutions. Owing to the power of RNA-guided destruction of nucleic acids, CRISPR-Cas system becomes a promising candidate for the development of the next-generation antimicrobials to deal with infectious diseases especially those caused by AMR pathogens (Figure 2A). The flexible programmability of the CRISPR-Cas system can selectively kill a particular bacterial member within a large population, which enables CRISPR-Cas antimicrobials to precisely modulate the composition of a complex bacterial population and will be extremely useful to treat infections within a natural complex microbial consortia, such as the gut microbiome. We summarize the major achievements of developing CRISPR-Cas antimicrobials to combat antimicrobial resistance with a focus on the type I, type II, and type VI systems
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