Antibacterial and Antibiofilm Activities of Novel Cyclic Peptides against Methicillin-Resistant Staphylococcus aureus

Methicillin-resistant Staphylococcus aureus (MRSA) has led to serious infections, especially in hospitals and clinics, where treatment and prevention have become more difficult due to the formation of biofilms. Owing to biofilm-derived antibiotic tolerance, the currently available traditional antibiotics have failed to treat MRSA infections. Hence, there is a urgent need to develop novel antibiotics for treating life-threatening MRSA infections. Lugdunin (cyclic peptide-1), a nonribosomal cyclic peptide produced by Staphylococcus lugdunensis, exhibits potent antimicrobial activity against MRSA. Amazingly, cyclic peptide-1 and its analogues cyclic peptide-11 and cyclic peptide-14 have the ability to disperse mature MRSA biofilms and show anti-clinical MRSA activity, including MRSA persister cells. In addition, these three cyclic peptide compounds have non-toxicity, lower hemolytic activity and lack of resistance development. Our results indicate that cyclic peptide-1, cyclic peptide-11, and cyclic peptide-14 have great potential as new antimicrobial drug candidates for the treatment of clinical MRSA infections.