摘要
细菌耐药性已成为全球关注的主要问题,影响了 22 个国家的约 500, 000 个人。因此,很明显,在这种情况下,革兰氏阴性菌受到了更多的关注。这些细菌执行多种抗性机制,例如将脂多糖中的脂质 A 修饰为 mcr-1 基因表达的产物。该基因最初是在动物中发现的;然而,它迅速传播到人类,传播到 70 个国家。 Mcr-1 基因对多粘菌素 B 和粘菌素具有抗性,这些药物被确定为对抗肠杆菌科细菌的最后替代品。尽管此类细菌的抗生素疗法普遍存在且缺乏抗生素疗法,但本文旨在汇编有关天然化合物抵抗由该基因引起的耐药性的信息,包括分离的粘菌素的活性或其与其他抗生素的关联。在评估粘菌素与其他化合物协同作用的研究中,叠氮胸苷和异戊内酯尤为突出。另一方面,paenipeptin 1 类似物与其他抗生素结合时表现出令人满意的活性。此外,值得一提的是,ostole 和丁子香酚之间针对磷酸乙醇胺转移酶 MCR-1 的分子对接结果表明,这些化合物可以与关键氨基酸残基相互作用,以促进该酶的催化作用。基于此,天然药物对 mcr-1 阳性细菌引起的感染的作用是显而易见的,直接有助于开发新的有效药物疗法。
关键词: MCR-1、磷酸乙醇胺转移酶、粘菌素、天然产物、细菌抗性、多粘菌素 B。
图形摘要
Current Drug Targets
Title:Revealing Insights into Natural Products Against mcr-1-Producing Bacteria
Volume: 22 Issue: 17
关键词: MCR-1、磷酸乙醇胺转移酶、粘菌素、天然产物、细菌抗性、多粘菌素 B。
摘要:
Bacterial resistance has become a major global concern, affecting about 500, 000 individuals in 22 countries. Thus, it is clear that Gram-negative bacteria have been receiving more attention in this scenario. These bacteria perform several resistance mechanisms, such as modifying lipid A from lipopolysaccharides as a product of the mcr-1 gene expression. This gene was initially identified in animals; however, it quickly spread to humans, spreading to 70 countries. Mcr-1 gene attributes resistance to polymyxin B and colistin, which are drugs established as the last alternative to combat Enterobacteriaceae bacteria.
Notwithstanding the prevalence and lack of antibiotic therapies for such bacteria, this article aimed to compile information about natural compounds against the resistance attributed by this gene, including the activity of isolated colistin or its associations with other antibiotics. Among the studies that evaluated colistin's synergistic action with other compounds, azidothymidine and isoalantholactone stood out. On the other hand, the paenipeptin 1 analog showed satisfactory activities when associated with other antibiotics. Besides, it is worth mentioning that molecular docking results between ostole and eugenol toward phosphoethanolamine transferase MCR-1 revealed that these compounds could interact with critical amino acid residues for the catalytic action of this enzyme. Based on this, natural agents' role is evident against infections caused by mcr-1-positive bacteria, directly contributing to the development of new effective pharmacotherapies.
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Cite this article as:
Revealing Insights into Natural Products Against mcr-1-Producing Bacteria, Current Drug Targets 2021; 22 (17) . https://dx.doi.org/10.2174/1389450122666210415102413
DOI https://dx.doi.org/10.2174/1389450122666210415102413 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
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