Document Type

Article

Version

Published Open Access

Publication Date

1-6-2017

Publication Title

PLoS One

DOI

10.1371/journal.pone.0169262

Abstract

In this report, we demonstrate the pH-dependent, in vitro antimicrobial activity of a cationic, amphiphilic random copolymer against clinical isolates of drug-resistant Staphylococcus aureus. The polymer was developed toward a long-term goal of potential utility in the treatment of skin infections. The proposed mechanism of action of the polymer is through selectively binding to bacterial membranes and subsequent disruption of the membrane structure/integrity, ultimately resulting in bacterial cell death. The polymer showed bactericidal activity against clinical isolates of methicillin-resistant or vancomycin-intermediate S. aureus. The polymer was effective in killing S. aureus at neutral pH, but inactive under acidic conditions (pH 5.5). The polymer did not exhibit any significant hemolytic activity against human red blood cells or display cytotoxicity to human dermal fibroblasts over a range of pH values (5.5-7.4). These results indicate that the polymer activity was selective against bacteria over human cells. Using this polymer, we propose a new potential strategy for treatment of skin infections using the pH-sensitive antimicrobial polymer agent that would selectively target infections at pH-neutral wound sites, but not the acidic, healthy skin.

Comments

Copyright: © 2017 Hong et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

Published Citation

Hong, S., Takahashi, H., Nadres, E. T., Mortazavian, H., Caputo, G. A., Younger, J. G., Kuroda, K. (2017) A Cationic Amphiphilic Random Copolymer with pH-Responsive Activity against Methicillin-Resistant Staphylococcus aureus. PLoS One 2(1): e0169262.

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