Endolysins and Their Potential in Combating Bacterial Multidrug Resistance.

Since the discovery of penicillin in 1928, more than a thousand antibiotics have been introduced into medical practice. Initially, the introduction of antibiotics revolutionized the treatment of infectious diseases. However, as antibiotics have been used repeatedly, scientists and clinicians have observed serious adverse consequences, most notably the emergence of bacterial resistance to antimicrobial agents. Of particular concern are multidrug-resistant pathogens, which are resistant to multiple antibiotic classes. As of 2024, antibiotic-resistant bacteria are directly responsible for approximately 1.27 million deaths worldwide. Thus, in response, possible new antibacterial agents are under investigation, including bacteriophages and the associated bacteriolytic enzymes. According to the World Health Organization (WHO), phage-based drugs are leading nonclassical antibiotics currently in clinical trials. Meanwhile, endolysins, as bacteriolytic phage enzymes, have emerged as promising antibacterial agents. This study reviews the key achievements and mechanisms of action of bacteriophage endolysins against bacterial infections, including biofilms, and discusses the therapeutic potential of endolysins in combating antibiotic resistance. Finally, the combined use of endolysins with other biomolecules and the application of artificial intelligence to address antimicrobial-resistant infections are also discussed.