Engineered Phage Enzymes Against Drug-resistant Pathogens: a Review on Advances and Applications

In recent decades, the expansion of multi and extensively drug-resistant (MDR and XDR) bacteria has reached an alarming rate, causing serious health concerns. Infections caused by drug-resistant bacteria have been associated with morbidity and mortality, making tackling bacterial resistance an urgent and unmet challenge that needs to be addressed properly. Endolysins are phage-encoded enzymes that can specifically degrade the bacterial cell wall and lead to bacterial death. There is remarkable evidence that corroborates the unique ability of endolysins to rapidly digest the peptidoglycan particular bonds externally without the assistance of phage. Thus, their modulation in therapeutic approaches has opened new options for therapeutic applications in the fight against bacterial infections in the human and veterinary sectors, as well as within the agricultural and biotechnology areas. The use of genetically engineered phage enzymes (EPE) promises to generate endolysin variants with unique properties for prophylactic and therapeutic applications. These approaches have gained momentum to accelerate basic as well as translational phage research and the potential development of therapeutics in the near future. This review will focus on the novel knowledge into EPE and demonstrate that EPE has far better performance than natural endolysins and phages in dealing with antibiotic-resistant infections. Therefore, it provides essential information for clinical trials involving EPE.