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A Choline-Recognizing Monomeric Lysin, ClyJ-3m, Shows Elevated Activity against Streptococcus pneumoniae
Dehua Luo1, Li Huang2, Vijay Singh Gondil3
1State Key Laboratory of Agricultural Microbiology, College of Life Science and Technology, Huazhong Agricultural University, Wuhan, China.
Antimicrobial Agents and Chemotherapy
|September 22, 2020
Summary
Engineered bacteriophage lysin ClyJ-3m, a monomer, shows enhanced bactericidal activity against Streptococcus pneumoniae. This novel lysin offers improved protection in infection models and better pharmacokinetic properties than its predecessor.
Area of Science:
- Microbiology
- Biochemistry
- Pharmacology
Background:
- * Streptococcus pneumoniae* is a major cause of bacterial pneumonia.
- * Bacteriophage lysins with choline-binding modules (CBMs) are effective antimicrobials.
- * ClyJ is a pneumococcus-specific lysin, with ClyJ-3 variant showing improved activity.
Purpose of the Study:
- * To engineer a novel variant of ClyJ-3, named ClyJ-3m, by deleting its C-terminal tail.
- * To evaluate the bactericidal activity and pharmacokinetic properties of ClyJ-3m.
- * To assess the therapeutic efficacy of ClyJ-3m in a *S. pneumoniae* bacteremia model.
Main Methods:
- * Construction and biochemical characterization of ClyJ-3m, a monomeric lysin.
- * In vitro assessment of bactericidal activity against various *S. pneumoniae* serotypes.
- * In vivo evaluation in a murine bacteremia model and pharmacokinetic analysis.
Main Results:
- * ClyJ-3m functions as a monomer upon choline binding, unlike the dimeric ClyJ-3.
- * ClyJ-3m demonstrated superior bactericidal activity against multiple pneumococcal strains.
- * ClyJ-3m provided significantly higher protection (70%) in a murine bacteremia model compared to ClyJ-3 (20%).
- * Pharmacokinetic studies showed ClyJ-3m has reduced clearance and a greater area under the curve than ClyJ-3.
Conclusions:
- * The engineered monomeric lysin ClyJ-3m exhibits enhanced bactericidal efficacy and improved pharmacokinetic profiles.
- * ClyJ-3m represents a promising therapeutic candidate for treating *Streptococcus pneumoniae* infections.
- * This study offers a novel strategy for designing and engineering bacteriophage lysins for targeted antimicrobial therapy.
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