Combination of Host Defense Peptide Mimicking Peptide Polymer and Proteinase K against Biofilms

Staphylococcus aureus (S. aureus) is one of the main pathogens causing urinary catheter-related infections, and its biofilm has strong resistance to immune clearance and antibiotics. Effective measures should be taken to solve catheter biofilm-related infections fundamentally. In this study, the host defense peptide mimicking peptide polymer was synthesized by rapid ring-opening polymerization of α-amino acid N-carboxyanhydride (NCA), which was initiated by lithium bis(trimethylsilyl)amide (LiHMDS). The resulting polymer showed a narrow molecular weight distribution. Antimicrobial experiment showed that this peptide polymer had a high bactericidal activity against the planktonic and persister cells of methicillin-resistant Staphylococcus aureus (MRSA). Bactericidal mechanism showed that this peptide polymer killed MRSA by destroying the integrity of bacterial cell membrane. Protein is one of the basic components of extracellular polymeric matrix (EPS), which plays an important role in bacterial colonization and biofilm development. The dispersing effect of proteinase K on EPS is beneficial to the penetration of antimicrobial agents into biofilms. 1.25 U/mL proteinase K dispersed mature MRSA biofilms in artificial urine, and the remaining cell viability was about 55% of the control group. The combination of proteinase K and polymer further eradicated mature MRSA biofilms in artificial urine, which confirmed the potential of synergism in eradicating the biofilms inside urinary catheter. The optimal combination reduced the cell viability within biofilms to about 10% of the control group.