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硝基还原酶在分枝杆菌生理学和药物敏感性中的作用。

Functions of nitroreductases in mycobacterial physiology and drug susceptibility.

作者信息

Eke Ifeanyichukwu E, Abramovitch Robert B

机构信息

Department of Microbiology, Genetics & Immunology, Michigan State University, East Lansing, Michigan, USA.

出版信息

J Bacteriol. 2025 Feb 20;207(2):e0032624. doi: 10.1128/jb.00326-24. Epub 2025 Jan 8.

DOI:10.1128/jb.00326-24
PMID:39772630
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11841060/
Abstract

Tuberculosis is a respiratory infection that is caused by members of the complex, with (Mtb) being the predominant cause of the disease in humans. The approval of pretomanid and delamanid, two nitroimidazole-based compounds, for the treatment of tuberculosis encourages the development of more nitro-containing drugs that target Mtb. Similar to the nitroimidazoles, many antimycobacterial nitro-containing scaffolds are prodrugs that require reductive activation into metabolites that inhibit the growth of the pathogen. This reductive activation is mediated by mycobacterial nitroreductases, leading to the hypothesis that these nitroreductases contribute to the specificity of the nitro prodrugs for mycobacteria. In addition to their prodrug-activating activities, these nitroreductases have different native activities that support the growth of the bacteria. This review summarizes the activities of different mycobacterial nitroreductases with respect to their activation of different nitro prodrugs and highlights their physiological functions in the bacteria.

摘要

结核病是一种由结核分枝杆菌复合群成员引起的呼吸道感染，其中结核分枝杆菌（Mtb）是人类该疾病的主要病因。两种基于硝基咪唑的化合物——普瑞玛胺和德拉马尼被批准用于治疗结核病，这推动了更多靶向Mtb的含氮药物的研发。与硝基咪唑类似，许多抗分枝杆菌含氮骨架是前药，需要还原激活成为抑制病原体生长的代谢物。这种还原激活由分枝杆菌硝基还原酶介导，由此提出了这些硝基还原酶有助于硝基前药对分枝杆菌特异性的假说。除了前药激活活性外，这些硝基还原酶还具有支持细菌生长的不同天然活性。本综述总结了不同分枝杆菌硝基还原酶对不同硝基前药的激活活性，并突出了它们在细菌中的生理功能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b3c/11841060/35a54e651e9b/jb.00326-24.f005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b3c/11841060/d4495d85569e/jb.00326-24.f001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b3c/11841060/12ee69d9e6b6/jb.00326-24.f002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b3c/11841060/8b02a575873d/jb.00326-24.f003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b3c/11841060/7b4d0592d250/jb.00326-24.f004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b3c/11841060/35a54e651e9b/jb.00326-24.f005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b3c/11841060/d4495d85569e/jb.00326-24.f001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b3c/11841060/12ee69d9e6b6/jb.00326-24.f002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b3c/11841060/8b02a575873d/jb.00326-24.f003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b3c/11841060/7b4d0592d250/jb.00326-24.f004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b3c/11841060/35a54e651e9b/jb.00326-24.f005.jpg

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