Journal
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
Volume 58, Issue 1, Pages 536-542Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/AAC.01793-13
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Funding
- Basic Research Program of the Ministry of Science and Technology of China [2012CB721102]
- National Natural Science Foundation of China [21075131]
- Post-Graduate Scientific and Technological Innovation Project of Chinese Academy of Sciences [Y204081YZ1]
- Key Laboratory on Emerging Infectious Diseases and Biosafety in Wuhan
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The treatment of infections caused by methicillin-resistant Staphylococcus aureus (MRSA) is a challenge worldwide. In our search for novel antimicrobial agents against MRSA, we constructed a chimeric lysin (named as ClyH) by fusing the catalytic domain of Ply187 (Pc) with the non-SH3b- like cell wall binding domain of phiNM3 lysin. Herein, the antimicrobial activity of ClyH against MRSA strains in vitro and in vivo was studied. Our results showed that ClyH could kill all of the tested clinical isolates of MRSA with higher efficacy than lysostaphin as well as its parental enzyme. The MICs of ClyH against clinical S. aureus strains were found to be as low as 0.05 to 1.61 mg/liter. In a mouse model, a single intraperitoneal administration of ClyH protected mice from death caused by MRSA, without obvious harmful effects. The present data suggest that ClyH has the potential to be an alternative therapeutic agent for the treatment of infections caused by MRSA.
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