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麦盖林:一种具有杀菌活性的酰基多胺。

Mygalin: An Acylpolyamine With Bactericidal Activity.

作者信息

Espinoza-Culupú Abraham, Mendes Elizabeth, Vitorino Hector Aguilar, da Silva Pedro Ismael, Borges Monamaris Marques

机构信息

Ph.D. Program in Biotechnology, University of São Paulo, São Paulo, Brazil.

Bacteriology Laboratory, Butantan Institute, São Paulo, Brazil.

出版信息

Front Microbiol. 2020 Jan 10;10:2928. doi: 10.3389/fmicb.2019.02928. eCollection 2019.

Abstract

Inappropriate use of antibiotics favors the selection and spread of resistant bacteria. To reduce the spread of these bacteria, finding new molecules with activity is urgent and necessary. Several polyamine analogs have been constructed and used to control microorganisms and tumor cells. Mygalin is a synthetic acylpolyamine, which are analogs of spermidine, derived from the hemolymph of the spider . The effective activity of polyamines and their analogs has been associated with their structure. The presence of two acyl groups in the Mygalin structure may give this molecule a specific antibacterial activity. The aim of this study was to identify the mechanisms involved in the interaction of Mygalin with to clarify its antimicrobial action. The results indicated that Mygalin exhibits intense dose and time-dependent bactericidal activity. Treatment of with this molecule caused membrane rupture, inhibition of DNA synthesis, DNA damage, and morphological changes. The esterase activity increased along with the intracellular production of reactive oxygen species (ROS) after treatment of the bacteria with Mygalin. In addition, this molecule was able to sequester iron and bind to LPS. We have shown that Mygalin has bactericidal activity with underlying mechanisms involving ROS generation and chelation of iron ions that are necessary for bacterial metabolism, which may contribute to its microbicidal activity. Taken together, our data suggest that Mygalin can be explored as a new alternative drug with antimicrobial potential against Gram-negative bacteria or other infectious agents.

摘要

抗生素的不当使用有利于耐药菌的选择和传播。为减少这些细菌的传播,迫切需要寻找具有活性的新分子。已经构建了几种多胺类似物并用于控制微生物和肿瘤细胞。Mygalin是一种合成酰基多胺,它是亚精胺的类似物,来源于蜘蛛的血淋巴。多胺及其类似物的有效活性与其结构有关。Mygalin结构中两个酰基的存在可能赋予该分子特定的抗菌活性。本研究的目的是确定Mygalin与……相互作用所涉及的机制,以阐明其抗菌作用。结果表明,Mygalin表现出强烈的剂量和时间依赖性杀菌活性。用该分子处理……导致膜破裂、DNA合成抑制、DNA损伤和形态变化。用Mygalin处理细菌后,酯酶活性随着细胞内活性氧(ROS)的产生而增加。此外,该分子能够螯合铁并与脂多糖结合。我们已经表明,Mygalin具有杀菌活性,其潜在机制涉及ROS的产生以及对细菌代谢所必需的铁离子的螯合,这可能有助于其杀菌活性。综上所述,我们的数据表明,Mygalin可以作为一种具有抗革兰氏阴性菌或其他感染因子潜力的新型替代药物进行探索。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f45/6965172/a4f3568abb93/fmicb-10-02928-g001.jpg

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