Cationic Methacrylate Polymers as Topical Antimicrobial Agents against Staphylococcus aureus Nasal Colonization

被引:98
|
作者
Thoma, Laura M. [1 ]
Boles, Blaise R. [2 ]
Kuroda, Kenichi [1 ,3 ]
机构
[1] Univ Michigan, Dept Chem, Ann Arbor, MI 48109 USA
[2] Univ Michigan, Dept Mol Cellular & Dev Biol, Ann Arbor, MI 48109 USA
[3] Univ Michigan, Sch Dent, Dept Biol & Mat Sci, Ann Arbor, MI 48109 USA
基金
美国国家科学基金会; 美国国家卫生研究院;
关键词
SUPPORTED LIPID-BILAYERS; MUPIROCIN RESISTANCE; KILLING KINETICS; SYNTHETIC MIMICS; HOLE FORMATION; CARRIAGE; PEPTIDES; MECHANISM; DESIGN; RISK;
D O I
10.1021/bm500557d
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The in vitro and in vivo antimicrobial activity of primary ammonium ethyl methacrylate homopolymers (AEMPs) was investigated. AEMPs with different degrees of polymerization (DP = 7.7-12) were prepared by reversible addition fragmentation chain-transfer (RAFT) polymerization. The AEMPs showed higher inhibitory effects against Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), than Gram-negative bacteria. The AEMPs also showed potent anti-S. aureus activity in the presence of fetal bovine serum, whereas the activity of the antibiotic mupirocin was reduced under the same conditions. The AEMPs showed very little or no hemolytic activity. The cytotoxicity of AEMPs against mammalian cells HEp-2 and COS-7 was concentration-dependent, and the cell viability significantly decreased at higher polymer concentrations. The AEMPs significantly reduced the number of viable S. aureus cells in the nasal environment of cotton rats when compared to that of the control. This study demonstrates that AEMPs have potential for use in treating topical S. aureus infections.
引用
收藏
页码:2933 / 2943
页数:11
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