|Title||ClyJ, a novel pneumococcal chimeric lysin with a CHAP catalytic domain.|
|Publication Type||Journal Article|
|Year of Publication||2019|
|Authors||Yang, H, Gong, Y, Zhang, H, Etobayeva, I, Miernikiewicz, P, Luo, D, Li, X, Zhang, X, Dabrowska, K, Nelson, DC, He, J, Wei, H|
|Journal||Antimicrob Agents Chemother|
|Date Published||2019 Jan 14|
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. Giving its high lytic activity and safety profile, ClyJ may represent a promising alternative to combat pneumococcal infections.
|Alternate Journal||Antimicrob. Agents Chemother.|