Advancing Beyond Antibiotics: The Pioneering Use of Bacteriophage Enzymes

The increasing prevalence of antibiotic-resistant bacterial infections necessitates the development of novel therapeutic methods. Bacteriophages, which are viruses that target bacteria, encode a variety of enzymes with potent antibacterial properties, which present a promising substitute for conventional antibiotics. Among these, phage-encoded peptidoglycan hydrolases (PGHs), such as virion-associated PGHs (VAPGHs) and endolysins, as well as polysaccharide depolymerases and holins, have been recognized as putative antibacterial agents. Endolysins, which are synthesized during the final stages of the phage replication process, degrade the cell wall of bacteria, resulting in cell lysis. The VAPGHs aid in initial cell wall penetration, while polysaccharide depolymerases target the bacterial cell wall envelope, assisting phage adsorption and host bacteria disintegration. Holins cause cytoplasmic membrane disruption, allowing the access of endolysin. Recent investigations in preclinical animal models have shown that these phage-derived enzymes are effective against a variety of bacterial infections, including multidrug-resistant strains. Engineered recombinant versions of these enzymes, developed to improve their bacteriolytic and bactericidal activity, have produced promising findings, implying a possible role in the fight against bacterial infections. This chapter discusses the therapeutic potential of phage-encoded enzymes, particularly in light of developing antibiotic resistance, emphasizing the need for further research and clinical development.