Phage engineering and phage-assisted CRISPR-Cas delivery to combat multidrug-resistant pathogens

Area of Science:

• Microbiology
• Molecular Biology
• Biotechnology

Background:

• Antibiotic resistance is a critical global health threat, driven by multidrug-resistant pathogens evading current therapies.
• Bacteriophages (phages), natural bacterial predators, were historically used therapeutically before antibiotics.
• Renewed interest in phages is spurred by the escalating crisis of antimicrobial resistance.

Purpose of the Study:

• To review strategies for engineering bacteriophages for therapeutic applications.
• To highlight the role of CRISPR-Cas9 in advancing phage genome engineering.
• To discuss methods for enhancing phage fitness, specificity, and lytic capabilities against bacterial infections.

Main Methods:

• Review of existing literature on bacteriophage biology and engineering techniques.
• Focus on clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 systems for precise phage genome modification.
• Exploration of methods to improve phage characteristics for enhanced therapeutic potential.

Main Results:

• CRISPR-Cas9 technology enables the generation of engineered bacteriophages with improved therapeutic properties.
• Engineered phages demonstrate enhanced specificity and efficacy in targeting bacterial pathogens.
• Various techniques can increase phage fitness, targeting precision, and lytic activity for infection control.

Conclusions:

• Bacteriophage engineering, particularly using CRISPR-Cas9, presents a viable strategy to combat antibiotic resistance.
• Tailored phage therapies can offer effective and specific alternatives to conventional antibiotics.
• Further development in phage engineering holds significant promise for addressing the challenge of antimicrobial resistance.