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镓(III)化合物的抗菌活性:对多种铁/血红素依赖性生物过程的病原体依赖性靶向作用

Antimicrobial Activity of Gallium(III) Compounds: Pathogen-Dependent Targeting of Multiple Iron/Heme-Dependent Biological Processes.

作者信息

Choi Seoung-Ryoung, Hassan Mohammed A, Britigan Bradley E, Narayanasamy Prabagaran

机构信息

Department of Pathology, Microbiology and Immunology, College of Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA.

Department of Internal Medicine, College of Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA.

出版信息

Curr Issues Mol Biol. 2024 Aug 22;46(8):9149-9161. doi: 10.3390/cimb46080541.

Abstract

Metals play vital roles in biological systems, with iron/heme being essential for cellular and metabolic functions necessary for survival and/or virulence in many bacterial pathogens. Given the rise of bacterial resistance to current antibiotics, there is an urgent need for the development of non-toxic and novel antibiotics that do not contribute to resistance to other antibiotics. Gallium, which mimics iron, has emerged as a promising antimicrobial agent, offering a novel approach to combat bacterial infections. Gallium does not have any known functions in biological systems. Gallium exerts its effects primarily by replacing iron in redox enzymes, effectively inhibiting bacterial growth by targeting multiple iron/heme-dependent biological processes and suppressing the development of drug resistance. The aim of this review is to highlight recent findings on the mechanisms of action of gallium and provide further insights into the development of gallium-based compounds. Understanding the mechanisms underlying gallium's biological activities is crucial for designing drugs that enhance their therapeutic therapies while minimizing side effects, offering promising avenues for the treatment of infectious diseases.

摘要

金属在生物系统中发挥着至关重要的作用,铁/血红素对于许多细菌病原体生存和/或致病所需的细胞及代谢功能至关重要。鉴于细菌对当前抗生素的耐药性不断增加,迫切需要开发无毒且新型的抗生素,这类抗生素不会导致对其他抗生素产生耐药性。模仿铁的镓已成为一种有前景的抗菌剂,为对抗细菌感染提供了一种新方法。镓在生物系统中没有任何已知功能。镓主要通过取代氧化还原酶中的铁来发挥作用,通过靶向多个铁/血红素依赖性生物过程有效抑制细菌生长,并抑制耐药性的产生。本综述的目的是强调镓作用机制的最新研究结果,并为基于镓的化合物的开发提供进一步的见解。了解镓生物活性的潜在机制对于设计既能增强治疗效果又能将副作用降至最低的药物至关重要,为传染病的治疗提供了有前景的途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/94ce/11352784/bda3fe151635/cimb-46-00541-g001.jpg

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