Polyglycerol-Based Macromolecular Iron Chelator Adjuvants for Antibiotics To Treat Drug-Resistant Bacteria
Polyglycerol-Based Macromolecular Iron Chelator Adjuvants for Antibiotics To Treat Drug-Resistant Bacteria
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DOI：
10.1021/acsami.0c06501
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发表时间：
2020-08-26
影响因子：
9.5
通讯作者：
Kizhakkedathu, Jayachandran N.
中科院分区：
文献类型：
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作者：
Abbina, Srinivas;Gill, Arshdeep;Kizhakkedathu, Jayachandran N.
铁是生命必需的微量营养素。它的氧化还原活性是许多重要酶促反应的关键组成部分，这些反应发生在药物代谢、DNA合成、类固醇合成、基因调控和细胞呼吸（氧转运和电子传递链）等过程中。细菌的生存和生长高度依赖于铁，并且具有获得铁的特定机制。限制铁对细菌的可用性，从而防止它们的生长，为在耐药性细菌持续上升的时代治疗感染提供了新的机会。在这项工作中，我们开发了大分子铁螯合剂，高亲和力铁螯合剂（HBEDS）与聚甘油的缀合物，试图螯合细菌的铁吸收，以限制它们的生长，从而提高抗生素活性。新型大分子螯合剂能有效地抑制金黄色葡萄球菌的生长，并对金黄色葡萄球菌有良好的抑菌作用。金黄色。此外，当与抗生素结合使用时，这些细胞相容性大螯合剂充当有效的佐剂以防止细菌生长。大螯合剂的佐剂活性取决于它们的分子量和这些分子上的螯合剂密度。这些选择性大分子铁（III）螯合剂在生长抑制和杀灭耐甲氧西林沙门氏菌方面非常有效。金黄色葡萄球菌联合低浓度利福平。
Iron is an essential micronutrient for life. Its redox activity is a key component in a plethora of vital enzymatic reactions that take place in processes such as drug metabolism, DNA synthesis, steroid synthesis, gene regulation, and cellular respiration (oxygen transport and the electron transport chain). Bacteria are highly dependent on iron for their survival and growth and have specific mechanisms to acquire iron. Limiting the availability of iron to bacteria, thereby preventing their growth, provides new opportunities to treat infection in the era of the persistent rise of antibiotic-resistant bacteria. In this work, we have developed macromolecular iron chelators, conjugates of a high-affinity iron chelator (HBEDS) with polyglycerol, in an attempt to sequester iron uptake by bacteria to limit their growth in order to enhance antibiotic activity. The new macromolecular chelators are successful in slowing the growth of Staphylococcus aureus and worked as an efficient bacteriostatic against S. aureus. Further, these cytocompatible macrochelators acted as effective adjuvants to prevent bacterial growth when used in conjunction with antibiotics. The adjuvant activity of the macrochelators depends on their molecular weight and the chelator density on these molecules. These selective macro iron(III) chelators are highly efficient in growth inhibition and killing of methicillin-resistant S. aureus in conjunction with a low concentration of rifampicin.