Choline-Recognizing Monomeric Lysin

By: Physician's Weekly Admin

Posted on: December 15, 2020

Choline-Recognizing Monomeric Lysin

lysins regularly function as choline-recognizing dimers. Streptococcus pneumoniae is a main microorganism for bacterial pneumonia, which can be treated with bacteriophage lysins holding a monitored choline restricting module (CBM). pneumococcus-explicit lysin ClyJ including the coupling demain from the putative endolysin gp20 from the Streptococcus phage SPSL1 and the CHAP (cysteine, histidine-subordinate amidohydrolase/peptidase) reactant domain from the PlyC lysin. Resembling typical CBM-containing lysins, ClyJ-3 dimerized upon binding with choline.  A variant of ClyJ with a shortened linker, i.e., ClyJ-3, shows improved activity and reduced cytotoxicity. Therefore in the results, we observed that biochemical characterization showed that ClyJ-3m remains a monomer after it binds to choline yet exhibits improved bactericidal activity against multiple pneumococcal strains with different serotypes. Pharmacokinetic analysis following single intravenously doses of 0.29 and 1.16 mg/kg of ClyJ-3 or ClyJ-3m in BALB/c mice revealed that ClyJ-3m shows a similar half-life but less clearance. Hence, to conclude it is evident that, choline-recognizing monomer ClyJ-3m exhibited enhanced bactericidal activity and improved pharmacokinetic proprieties compared to those of its parental ClyJ-3 lysin.