Bacteriophage endolysins: A promising therapeutic strategy against drug- resistant Staphylococcus aureus

Staphylococcus aureus infections are difficult to treat due to the widespread emergence of antibiotic resistant strains, complex virulence mechanisms, and the ability to form recalcitrant biofilms. Infections with multi-drug resistant variants such as the methicillin resistant S. aureus (MRSA) and vancomycin-resistant S. aureus (VRSA) lead to increased morbidity and mortality and result in higher treatment cost compared to those with sensitive strains. While vaccines are sought as a preventive strategy, a clinically viable vaccine has not surfaced yet. Considering the rapid dissemination of resistant strains across the globe, the World Health Organisation has categorised S. aureus as an ESKAPE pathogen that requires the immediate development of alternative therapeutics. One of the most promising alternative to conventional antibiotics are bacteriophage endolysins, a family of peptidoglycan hydrolases capable of destabilising the peptidoglycan cell wall in bacteria by cleaving essential bonds in the peptidoglycan structure. Bacteriophages employ these for lysing the host cell during the last stage of their lytic life cycle to release progeny virions. A study published in 2001 demonstrated that purified endolysins can lyse bacterial cells rapidly and effectively when administered exogenously. Endolysins offer many advantages over conventional antibiotics: they are not likely to develop resistance as they target a highly conserved and indispensable component of the bacterial cell wall; they act faster than conventional antibiotics; they are species-selective in their lytic activity, sparing non-target organisms. Despite the numerous challenges in their clinical deployment, a large number of phage endolysins have been studied for their antibacterial potential against bacterial pathogens, including S. aureus. The present chapter provides a comprehensive account of the various endolysins, natural and engineered, studied as antimicrobial agents against drug resistant S. aureus.