Methicillin-resistant Staphylococcus aureus (MRSA) has been one of the major nosocomial pathogens to cause frequent and serious infections that are associated with various biomedical surfaces. This study demonstrated that surface modified with host defense peptide-mimicking β-peptide polymer, has surprisingly high bactericidal activities against Escherichia coli ( E. coli) and MRSA. As surface-tethered β-peptide polymers cannot move freely to adopt the collaborative interactions with bacterial membrane and are too short to penetrate the cell envelop, we proposed a mode of action by diffusing away the cell membrane-stabilizing divalent ions, Ca and Mg. This hypothesis was supported by our study that Ca and Mg supplementation in the assay medium causes up to 80% loss of bacterial killing efficacy and that the addition of divalent ion chelating ethylenediaminetetraacetic acid into the above assay medium leads to significant recovery of the bacterial killing efficacy. In addition to its potent bacterial killing efficacy, the surface-tethered β-peptide polymer also demonstrated excellent biocompatibility by displaying no hemolysis and supporting mammalian cell adhesion and growth. In conclusion, this study demonstrated the potential of β-peptide polymer-modified surface in addressing nosocomial infections that are associated with various surfaces in biomedical applications.

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