title: A Cationic Amphiphilic Random Copolymer with pH-Responsive Activity against Methicillin-Resistant Staphylococcus aureus.
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.
authors.affiliation: Department of Emergency Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Sungyoup
authors.identifier: http://orcid.org/0000-0002-3387-6194
authors.initials: S
authors.lastname: Hong
authors.affiliation: Department of Biologic and Materials Sciences, University of Michigan School of Dentistry, Ann Arbor, Michigan, United States of America.
authors.forename: Haruko
authors.initials: H
authors.lastname: Takahashi
authors.affiliation: Department of Biologic and Materials Sciences, University of Michigan School of Dentistry, Ann Arbor, Michigan, United States of America.
authors.forename: Enrico T
authors.initials: ET
authors.lastname: Nadres
authors.affiliation: Department of Biologic and Materials Sciences, University of Michigan School of Dentistry, Ann Arbor, Michigan, United States of America.
authors.forename: Hamid
authors.initials: H
authors.lastname: Mortazavian
authors.affiliation: Department of Chemistry and Biochemistry, Rowan University, Glassboro, New Jersey, United States of America.
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Caputo
authors.affiliation: Department of Emergency Medicine, University of Michigan Medical School, Ann Arbor, Michigan, United States of America.
authors.forename: John G
authors.initials: JG
authors.lastname: Younger
authors.affiliation: Department of Biologic and Materials Sciences, University of Michigan School of Dentistry, Ann Arbor, Michigan, United States of America.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Kuroda
mesh_terms: D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology*; D002478:Cells, Cultured; D004912:Erythrocytes / Q000187:drug effects; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D006863:Hydrogen-Ion Concentration; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D016712:Mupirocin / Q000494:pharmacology; D011108:Polymers / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology; D013211:Staphylococcus aureus / Q000187:drug effects; D014640:Vancomycin / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D011108:Polymers; D014640:Vancomycin; D016712:Mupirocin