title: Novel chimeric lysin with high-level antimicrobial activity against methicillin-resistant Staphylococcus aureus in vitro and in vivo.
abstract: 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.
authors.affiliation: State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.
authors.forename: Hang
authors.initials: H
authors.lastname: Yang
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhang
authors.forename: Junping
authors.initials: J
authors.lastname: Yu
authors.forename: Yanling
authors.initials: Y
authors.lastname: Huang
authors.forename: Xian-En
authors.initials: XE
authors.lastname: Zhang
authors.forename: Hongping
authors.initials: H
authors.lastname: Wei
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects* / Q000472:pathogenicity*; D051379:Mice; D008807:Mice, Inbred BALB C; D008826:Microbial Sensitivity Tests; D009088:Mucoproteins / Q000494:pharmacology / Q000627:therapeutic use*; D013203:Staphylococcal Infections / Q000188:drug therapy*
chemical_list: D000890:Anti-Infective Agents; D009088:Mucoproteins; C010393:lysin, gastropoda