Trio Act of Boronolectin with Antibiotic-Metal Complexed Macromolecules toward Broad-Spectrum Antimicrobial Efficacy,ACS Infectious Diseases

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Trio Act of Boronolectin with Antibiotic-Metal Complexed Macromolecules toward Broad-Spectrum Antimicrobial Efficacy
ACS Infectious Diseases ( IF 4.0 ) Pub Date : 2017-10-06 00:00:00 , DOI: 10.1021/acsinfecdis.7b00132
Peng Yang ₁ , Marpe Bam ₂ , Parasmani Pageni ₁ , Tianyu Zhu ₁ , Yung Pin Chen ₃ , Mitzi Nagarkatti ₂ , Alan W. Decho ₃ , Chuanbing Tang ₁

Affiliation

Bacterial infections, particularly by Gram-negative pathogens, have become a serious threat to global healthcare due to the diminishing effectiveness of existing antibiotics. We report a nontraditional therapy to combine three components in one macromolecular system, in which boronic acid adheres to peptidoglycan or lipopolysaccharide via boron-polyol based boronolectin chemistry, cationic metal polymer frameworks interact with negatively charged cell membranes, and β-lactam antibiotics are reinstated with enhanced vitality to attack bacteria via evading the detrimental enzyme-catalyzed hydrolysis. These macromolecular systems exhibited high efficacy in combating pathogenic bacteria, especially Gram-negative strains, due to synergistic effects of multicomponents on interactions with bacterial cells. In vitro and in vivo cytotoxicity and hemolysis evaluation indicated that these multifunctional copolymers did not induce cell death by apoptosis, as well as did not alter the phenotypes of immune cells and did not show observable toxic effect on red blood cells.

中文翻译：

硼铁蛋白与抗生素-金属复合大分子对广谱抗菌功效的三重作用

由于现有抗生素的有效性下降，细菌感染，尤其是革兰氏阴性病原体的细菌感染已成为全球医疗保健的严重威胁。我们报告了一种非传统疗法，可在一个大分子系统中结合三种成分，其中硼酸通过基于硼多元醇的硼酸凝集素化学粘附在肽聚糖或脂多糖上，阳离子金属聚合物骨架与带负电荷的细胞膜相互作用，而β-内酰胺类抗生素则被恢复为通过避免有害的酶催化水解作用，增强了攻击细菌的活力。由于多组分对与细菌细胞相互作用的协同作用，这些大分子系统在对抗病原细菌，特别是革兰氏阴性菌株方面显示出很高的功效。体外和体内细胞毒性和溶血评价表明，这些多官能共聚物没有通过细胞凋亡诱导细胞死亡，以及不改变免疫细胞的表型并没有表现出对红细胞的可观察到的毒性作用。

更新日期：2017-10-06

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