Antimicrobial Metallopolymers and Their Bioconjugates with Conventional Antibiotics against Multidrug-Resistant Bacteria

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• 作者：Jiuyang Zhang ; Yung Pin Chen ; Kristen P. Miller ; Mitra S. Ganewatta ; Marpe Bam ; Yi Yan ; Mitzi Nagarkatti ; Alan W. Decho ; Chuanbing Tang
• 刊名：Journal of the American Chemical Society
• 出版年：2014
• 出版时间：April 2, 2014
• 年：2014
• 卷：136
• 期：13
• 页码：4873-4876
• 全文大小：343K
• 年卷期：v.136,no.13(April 2, 2014)
• ISSN：1520-5126

文摘

Bacteria are now becoming more resistant to most conventional antibiotics. Methicillin-resistant Staphylococcus aureus (MRSA), a complex of multidrug-resistant Gram-positive bacterial strains, has proven especially problematic in both hospital and community settings by deactivating conventional 尾-lactam antibiotics, including penicillins, cephalosporins, and carbapenems, through various mechanisms, resulting in increased mortality rates and hospitalization costs. Here we introduce a class of charged metallopolymers that exhibit synergistic effects against MRSA by efficiently inhibiting activity of 尾-lactamase and effectively lysing bacterial cells. Various conventional 尾-lactam antibiotics, including penicillin-G, amoxicillin, ampicillin, and cefazolin, are protected from 尾-lactamase hydrolysis via the formation of unique ion-pairs between their carboxylate anions and cationic cobaltocenium moieties. These discoveries could provide a new pathway for designing macromolecular scaffolds to regenerate vitality of conventional antibiotics to kill multidrug-resistant bacteria and superbugs.