Enzybiotics: Enzyme-Based Antibacterials as Therapeutics.

Antibiotics have saved millions of lives. However, the overuse and misuse of antibiotics have contributed to a rapid emergence of antibiotic resistance worldwide. In addition, there is an unprecedented void in the development of new antibiotic classes by the pharmaceutical industry since the first introduction of antibiotics. This antibiotic crisis underscores the urgent and increasing necessity of new, innovative antibiotics. Enzybiotics are such a promising class of antibiotics. They are derived from endolysins, bacteriophage-encoded enzymes that degrade the bacterial cell wall of the infected cell at the end of the lytic replication cycle. Enzybiotics are featured by a rapid and unique mode-of-action, a high specificity to kill pathogens, a low probability for bacterial resistance development and a proteinaceous nature. (Engineered) endolysins have been demonstrated to be effective in a variety of animal models to combat both Gram-positive and Gram-negative bacteria and have entered different phases of preclinical and clinical trials. In addition, mycobacteriophage-encoded endolysins have been successfully used to inhibit mycobacteria in vitro. In this chapter we focus on the (pre)clinical progress of enzybiotics as potent therapeutic agent against human pathogenic bacteria.