Enantiomeric Glycosylated Cationic Block Co-Beta-Peptides Eradicate Antibiotic-Tolerant Persisters and Biofilm in Staphylococcus Aureus

The treatment of bacterial infection is hindered by the presence of biofilm and metabolically inactive persisters. Methicillin-resistant Staphylococcus aureus (MRSA) is a major pathogen causing mortality and morbidity due to infections. We have synthesized a new enantiomeric block co-beta-peptide, (PDGu(7)-b-PBLK(13)), with high yield and purity by a one-shot one-pot anionic-ring opening (co)polymerization (AROP). The co-beta-peptide is bactericidal against replicating as well as biofilm and persisters MRSA, and also disperses biofilm biomass. Its antibacterial activity is superior to vancomycin in established MRSA murine and human ex vivo skin infection models, with no acute in vivo toxicity in repeated dosing in mice at above therapeutic levels. This new class of non-toxic molecule, effective against all bacterial sub-populations, has promising clinical potential.