The emergence of antimicrobial-resistant (AMR) bacteria poses an imminent threat to our society and requires urgent actions. We here propose that a bacteriophage-derived protein called endolysin can be exploited as a new antimicrobial agent to tackle this global public heath issue. Endolysins are hydrolytic enzymes that cleave bacterial cell-walls (peptidoglycan layers), allowing for rapid cell lysis in a matter of minutes. Not only this swift response makes a stark contrast with conventional antibiotics, but the protein nature of endolysins makes them amenable to modifications. For example, modular domains of endolysin can be recombined to create new artificial endolysins. Using in-house high-throughput screening system, we show that we can quickly discover multiple endolysins against methicillin-resistant Staphylococcus aureus (MRSA) with improved activity compared to previously reported ones. We also discuss the prospects for the development of antimicrobial endolysins against any potential pathogens using our proprietary microbial single-cell genome sequencing platform, bit-MAP(R).