A novel chimeric lysin with robust antibacterial activity against planktonic and biofilm methicillin-resistant Staphylococcus aureus

Hang Yang,Jing Wang,Hongping Wei,Huaidong Zhang,Junping Yu

doi:10.1038/srep40182

Abstract

Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most threatening pathogens due to its multi-drug resistance (MDR) and strong biofilm-forming capacity. Here, we described the screening of a novel chimeolysin (ClyF) that was active against planktonic and biofilm MRSA. Biochemical tests showed that ClyF was active against all S. aureus clinical isolates tested under planktonic and biofilm conditions. Structure analysis revealed that ClyF has an enhanced thermostability and pH tolerance than its parental lysin Pc by forming a hydrophobic cleft in the catalytic domain and an Ig-like structure in the cell-wall binding domain. A single intraperitoneally or topically administration of ClyF showed good MRSA removing efficacy in mouse models of bacteremia and burn wound infection, respectively. Our data collectively demonstrated that ClyF has good bactericidal activity against planktonic and biofilm MRSA both in vitro and in vivo, and therefore represents a useful antibacterial to combat MDR S. aureus.

Highlights

In the present study, a novel staphylolytic chimeolysin, ClyF, was identified using the screening method, and its bactericidal activity against planktonic and biofilm MRSA was further ascertained in vitro and in vivo in mouse models of bacteremia and burn wound infection
There are no lysin-derived drugs on the market yet, the recent progresses in clinical trials for two staphylococcal lysins (i.e. CF-30130 and P12831) suggest bright potential for treating bacterial infections by lysins
We described the rapid screening of chimeolysins against staphylococci by using the induced lysis-based screening method

Summary

Introduction

A novel staphylolytic chimeolysin, ClyF, was identified using the screening method, and its bactericidal activity against planktonic and biofilm MRSA was further ascertained in vitro and in vivo in mouse models of bacteremia and burn wound infection. Results showed that the activity of Clys[114] (ClyF) against S. aureus N315 was much higher (10–87 folds faster) than that of these four chimeolysins, quite consistent with the observations on the screening plates (Fig. 4A).

Results

Conclusion