Bacteriophage-Derived Enzymes as Potential Alternatives for the Treatment of MDR Bacterial Infections

Bacteriophage lytic enzymes, also known as lysins, are highly evolved chemicals that are produced by bacteriophage to break down bacterial cell walls and release their progeny. These enzymes, known as “enzybiotics,” have an antibacterial property due to their ability to degrade peptidoglycan, a crucial part of the bacterial cell wall. Phage lytic products kill the target bacteria when introduced exogenously as recombinant proteins. Gram-positive bacteria immediately lyse when small amounts of purified recombinant lysin are added, which causes the target bacterium to die log-fold. Lysins have been successfully employed in animal studies to combat pathogenic antibiotic-resistant bacteria. Their distinct mechanism of action is responsible for their quick action, potent bactericidal impact, absence of resistance development, and activity against persister cells. Thus, in a time when antibiotic resistance is increasing, lysins may be a useful anti-infective. This chapter thoroughly overviews the therapeutic application and eventual development of phage-encoded lysins as novel anti-infectives. It also describes the limitations of both agents with regard to their composition, specificity, mechanism of action, emergence of resistance, method of product production, and how they interact with the immune system.