Bacteriophage endolysins as a potential weapon to combat Clostridioides difficile infection

Clostridioides difficile is the leading cause of health-care-associated infection throughout the developed world and contributes significantly to patient morbidity and mortality. Typically, antibiotics are used for the primary treatment of C. difficile infections (CDIs), but they are not universally effective for all ribotypes and can result in antibiotic resistance and recurrent infection, while also disrupting the microbiota. Novel targeted therapeutics are urgently needed to combat CDI. Bacteriophage-derived endolysins are required to disrupt the bacterial cell wall of their target bacteria and are possible alternatives to antibiotics. These lytic proteins could potentially replace or augment antibiotics in CDI treatment. We discuss candidate therapeutic lysins derived from phages/prophages of C. difficile and their potential as antimicrobials against CDI. Additionally, we review the antibacterial potential of some recently identified homologues of C. difficile endolysins. Finally, the challenges of endolysins are considered with respect to the development of novel lysin-based therapies.