Polymers for binding of the gram-positive oral pathogen Streptococcus mutans.
Polymers for binding of the gram-positive oral pathogen Streptococcus mutans.
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DOI：
10.1371/journal.pone.0180087
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Mantovani G
中科院分区：
文献类型：
--
作者：
Magennis EP;Francini N;Mastrotto F;Catania R;Redhead M;Fernandez-Trillo F;Bradshaw D;Churchley D;Winzer K;Alexander C;Mantovani G
变形链球菌是与龋齿形成有关的最重要的致病菌，直接或间接地与多发性硬化症、脑血管和外周动脉疾病等严重疾病有关。能够选择性地结合变形链球菌和/或以非致命性方式抑制其与口腔组织的黏附的聚合物将提供解决致病性的可能性，而不需要选择对杀菌剂具有耐药性的群体。本工作合成了N，N，N-三甲基乙胺阳离子基团和磺基甜菜碱两性离子基团不同比例的2-(二甲氨基)甲基丙烯酸乙酯(PDMAEMA)聚合物。这些共聚物最初被测试为变形链球菌NCTC 10449的潜在大分子配体，而大肠杆菌MG1655被用作革兰氏阴性对照细菌。具有高比例两性离子重复单元的pDMAEMA衍生材料在分离和变形链球菌-大肠杆菌混合培养中都被发现对变形链球菌具有选择性。随后发现，与革兰氏阴性大肠埃希菌和哈维氏弧菌相比，完全磺化的pDMAEMA优先结合/聚集革兰氏阳性变形链球菌和金黄色葡萄球菌。变形链球菌致病的关键初始阶段涉及凝集素介导的牙面黏附，因此通过研究含有α-甘露糖苷和β-半乳糖苷侧链单元的两种糖共聚物，进一步扩大了潜在的大分子配体的范围。与这些聚合物的结果表明，通过调节所选多价配体的糖基化模式，可以优先与变形链球菌或大肠杆菌结合，而不会在模型胃肠道细胞系中引起不可接受的细胞毒性。总体而言，我们的结果能够确定所研究的潜在抗菌聚合物的结构-性质关系，并表明可以通过微调聚合物配体中的识别元件来实现与革兰氏阳性变形链球菌的优先结合。
Streptococcus mutans is the most significant pathogenic bacterium implicated in the formation of dental caries and, both directly and indirectly, has been associated with severe conditions such as multiple sclerosis, cerebrovascular and peripheral artery disease. Polymers able to selectively bind S. mutans and/or inhibit its adhesion to oral tissue in a non-lethal manner would offer possibilities for addressing pathogenicity without selecting for populations resistant against bactericidal agents. In the present work two libraries of 2-(dimethylamino)ethyl methacrylate (pDMAEMA)-based polymers were synthesized with various proportions of either N,N,N-trimethylethanaminium cationic- or sulfobetaine zwitterionic groups. These copolymers where initially tested as potential macromolecular ligands for S. mutans NCTC 10449, whilst Escherichia coli MG1655 was used as Gram-negative control bacteria. pDMAEMA-derived materials with high proportions of zwitterionic repeating units were found to be selective for S. mutans, in both isolated and S. mutans–E. coli mixed bacterial cultures. Fully sulfobetainized pDMAEMA was subsequently found to bind/cluster preferentially Gram-positive S. mutans and S. aureus compared to Gram negative E. coli and V. harveyi. A key initial stage of S. mutans pathogenesis involves a lectin-mediated adhesion to the tooth surface, thus the range of potential macromolecular ligands was further expanded by investigating two glycopolymers bearing α-mannopyranoside and β-galactopyranoside pendant units. Results with these polymers indicated that preferential binding to either S. mutans or E. coli can be obtained by modulating the glycosylation pattern of the chosen multivalent ligands without incurring unacceptable cytotoxicity in a model gastrointestinal cell line. Overall, our results allowed to identify a structure–property relationship for the potential antimicrobial polymers investigated, and suggest that preferential binding to Gram-positive S. mutans could be achieved by fine-tuning of the recognition elements in the polymer ligands.