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.
The Middle East respiratory syndrome coronavirus (MERS-CoV) was first isolated in 2012, and circulated worldwide with high mortality. The continual outbreaks of MERS-CoV highlight the importance of developing antiviral therapeutics. Here, we rationally designed a novel fusion inhibitor named MERS-five-helix bundle (MERS-5HB) derived from the six-helix bundle (MERS-6HB) which was formed by the process of membrane fusion. MERS-5HB consists of three copies of heptad repeat 1 (HR1) and two copies of heptad repeat 2 (HR2) while MERS-6HB includes three copies each of HR1 and HR2. As it lacks one HR2, MERS-5HB was expected to interact with viral HR2 to interrupt the fusion step. What we found was that MERS-5HB could bind to HR2P, a peptide derived from HR2, with a strong affinity value (KD) of up to 0.24 nM. Subsequent assays indicated that MERS-5HB could inhibit pseudotyped MERS-CoV entry effectively with 50% inhibitory concentration (IC50) of about 1 μM. In addition, MERS-5HB significantly inhibited spike (S) glycoprotein-mediated syncytial formation in a dose-dependent manner. Further biophysical characterization showed that MERS-5HB was a thermo-stable α-helical secondary structure. The inhibitory potency of MERS-5HB may provide an attractive basis for identification of a novel inhibitor against MERS-CoV, as a potential antiviral agent.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.