ClyJ Is a Novel Pneumococcal Chimeric Lysin with a Cysteine- and Histidine-Dependent Amidohydrolase/Peptidase Catalytic Domain.

is one of the leading pathogens that cause a variety of mucosal and invasive infections. With the increased emergence of multidrug-resistant ， new antimicrobials with mechanisms of action different from conventional antibiotics are urgently needed. In this study， we identified a putative lysin (gp20) encoded by the phage SPSL1 using the LytA autolysin as a template. Molecular dissection of gp20 revealed a binding domain (GPB) containing choline-binding repeats (CBRs) that are high specificity for By fusing GPB to the CHAP (cysteine， histidine-dependent amidohydrolase/peptidase) catalytic domain of the PlyC lysin， we constructed a novel chimeric lysin， ClyJ， with improved activity to the pneumococcal Cpl-1 lysin. No resistance was observed in strains after exposure to incrementally doubling concentrations of ClyJ for 8 continuous days In a mouse bacteremia model using penicillin G as a control， a single intraperitoneal injection of ClyJ improved the survival rate of lethal -infected mice in a dose-dependent manner. Given its high lytic activity and safety profile， ClyJ may represent a promising alternative to combat pneumococcal infections.