Star-Peptide Polymers are Multi-Drug-Resistant Gram-Positive Bacteria Killers
Wenyi Li, Sara Hadjigol, Alicia Rasines Mazo, James A. Holden, Jason C. Lenzo, Steven J. Shirbin, Anders J. Barlow, Sadegh Shabani, Tao Huang, Eric C. Reynolds, Greg G. Qiao, Neil M. O’Brien‐Simpson
Abstract
Antibiotic resistance in bacteria, especially Gram-positive bacteria like Staphylococcus aureus, is gaining considerable momentum worldwide and unless checked will pose a global health crisis. With few new antibiotics coming on the market, there is a need for novel antimicrobial materials that target and kill multi-drug-resistant (MDR) Gram-positive pathogens like methicillin-resistant Staphylococcus aureus (MRSA). In this study, using a novel mixed-bacteria antimicrobial assay, we show that the star-peptide polymers preferentially target and kill Gram-positive pathogens including MRSA. A major effect on the activity of the star-peptide polymer was structure, with an eight-armed structure inducing the greatest bactericidal activity. The different star-peptide polymer structures were found to induce different mechanisms of bacterial death both in vitro and in vivo. These results highlight the potential utility of peptide/polymers to fabricate materials for therapeutic development against MDR Gram-positive bacterial infections.