ClyJ, a novel pneumococcal chimeric lysin with a CHAP catalytic domain.

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TitleClyJ, a novel pneumococcal chimeric lysin with a CHAP catalytic domain.
Publication TypeJournal Article
Year of Publication2019
AuthorsYang, H, Gong, Y, Zhang, H, Etobayeva, I, Miernikiewicz, P, Luo, D, Li, X, Zhang, X, Dabrowska, K, Nelson, DC, He, J, Wei, H
JournalAntimicrob Agents Chemother
Date Published2019 Jan 14
ISSN1098-6596
Abstract

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.

DOI10.1128/AAC.02043-18
Alternate JournalAntimicrob. Agents Chemother.
PubMed ID30642930