结核分枝杆菌中心碳代谢：一个意想不到的前沿领域。
Central carbon metabolism in Mycobacterium tuberculosis: an unexpected frontier.
机构信息
Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA.
出版信息
Trends Microbiol. 2011 Jul;19(7):307-14. doi: 10.1016/j.tim.2011.03.008. Epub 2011 May 10.
Abstract
Recent advances in liquid chromatography and mass spectrometry have enabled the highly parallel, quantitative measurement of metabolites within a cell and the ability to trace their biochemical fates. In Mycobacterium tuberculosis (Mtb), these advances have highlighted major gaps in our understanding of central carbon metabolism (CCM) that have prompted fresh interpretations of the composition and structure of its metabolic pathways and the phenotypes of Mtb strains in which CCM genes have been deleted. High-throughput screens have demonstrated that small chemical compounds can selectively inhibit some enzymes of Mtb's CCM while sparing homologs in the host. Mtb's CCM has thus emerged as a frontier for both fundamental and translational research.
摘要
近年来，液相色谱和质谱技术的发展使得在细胞内进行代谢物的高通量、定量测量以及追踪其生化命运成为可能。在结核分枝杆菌（Mtb）中，这些进展凸显了我们对中心碳代谢（CCM）理解的主要空白，促使人们对其代谢途径的组成和结构以及 CCM 基因缺失的 Mtb 菌株的表型进行了新的解释。高通量筛选表明，小分子化合物可以选择性地抑制 Mtb 的 CCM 中的一些酶，而宿主中的同源物则不受影响。因此，Mtb 的 CCM 成为基础和转化研究的前沿。
相似文献
1
Central carbon metabolism in Mycobacterium tuberculosis: an unexpected frontier.结核分枝杆菌中心碳代谢：一个意想不到的前沿领域。
Trends Microbiol. 2011 Jul;19(7):307-14. doi: 10.1016/j.tim.2011.03.008. Epub 2011 May 10.
2
Iron limitation in M. tuberculosis has broad impact on central carbon metabolism.结核分枝杆菌中的铁限制对中心碳代谢有广泛影响。
Commun Biol. 2022 Jul 9;5(1):685. doi: 10.1038/s42003-022-03650-z.
3
Assessing the progress of Mycobacterium tuberculosis H37Rv structural genomics.评估结核分枝杆菌H37Rv结构基因组学的进展。
Tuberculosis (Edinb). 2015 Mar;95(2):131-6. doi: 10.1016/j.tube.2014.12.005. Epub 2014 Dec 31.
4
Metabolomics of Mycobacterium tuberculosis reveals compartmentalized co-catabolism of carbon substrates.结核分枝杆菌的代谢组学揭示了碳底物的区室化共分解代谢。
Chem Biol. 2010 Oct 29;17(10):1122-31. doi: 10.1016/j.chembiol.2010.08.009.
5
Mycobacterial genes essential for the pathogen's survival in the host.分枝杆菌在宿主体内存活所必需的基因。
Immunol Rev. 2015 Mar;264(1):319-26. doi: 10.1111/imr.12256.
6
Comparative genomics shows differences in the electron transport and carbon metabolic pathways of Mycobacterium africanum relative to Mycobacterium tuberculosis and suggests an adaptation to low oxygen tension.比较基因组学显示，非洲分枝杆菌相对于结核分枝杆菌在电子传递和碳代谢途径上存在差异，并表明其对低氧张力的适应。
Tuberculosis (Edinb). 2020 Jan;120:101899. doi: 10.1016/j.tube.2020.101899. Epub 2020 Jan 8.
7
Glucose phosphorylation is required for Mycobacterium tuberculosis persistence in mice.葡萄糖磷酸化是结核分枝杆菌在小鼠体内持续存在所必需的。
PLoS Pathog. 2013 Jan;9(1):e1003116. doi: 10.1371/journal.ppat.1003116. Epub 2013 Jan 10.
8
Isocitrate lyase mediates broad antibiotic tolerance in Mycobacterium tuberculosis.异柠檬酸裂解酶介导结核分枝杆菌广泛的抗生素耐受。
Nat Commun. 2014 Jun 30;5:4306. doi: 10.1038/ncomms5306.
9
Metabolomics of Central Carbon Metabolism in Mycobacterium tuberculosis.结核分枝杆菌中心碳代谢的代谢组学研究。
Microbiol Spectr. 2014 Jun;2(3). doi: 10.1128/microbiolspec.MGM2-0026-2013.
10
The Sculpting of the Mycobacterium tuberculosis Genome by Host Cell-Derived Pressures.宿主细胞衍生压力对结核分枝杆菌基因组的塑造。
Microbiol Spectr. 2014 Oct;2(5). doi: 10.1128/microbiolspec.MGM2-0016-2013.
引用本文的文献
1
Mycobacterium tuberculosis curli pili facilitates pathogenicity by modulating central carbon metabolism.结核分枝杆菌卷曲菌毛通过调节中心碳代谢促进致病性。
Metabolomics. 2025 Aug 12;21(5):118. doi: 10.1007/s11306-025-02320-5.
2
Trehalose catalytic shift inherently enhances phenotypic heterogeneity and multidrug resistance in Mycobacterium tuberculosis.海藻糖催化转变内在地增强了结核分枝杆菌的表型异质性和多药耐药性。
Nat Commun. 2025 Jul 11;16(1):6442. doi: 10.1038/s41467-025-61703-3.
3
Mycobacterium tuberculosis curli pili (MTP) and heparin-binding hemagglutinin adhesin (HBHA) facilitate regulation of central carbon metabolism, enhancement of ATP synthesis and cell wall biosynthesis.结核分枝杆菌卷曲菌毛（MTP）和肝素结合血凝素黏附素（HBHA）有助于调节中心碳代谢、增强ATP合成及细胞壁生物合成。
Arch Microbiol. 2025 May 28;207(7):156. doi: 10.1007/s00203-025-04352-w.
4
An integrated structural and biophysical approach to study carbon metabolism in .一种综合的结构和生物物理方法来研究……中的碳代谢
QRB Discov. 2025 Mar 12;6:e15. doi: 10.1017/qrd.2025.6. eCollection 2025.
5
Trehalose catalytic shift is an intrinsic factor in Mycobacterium tuberculosis that enhances phenotypic heterogeneity and multidrug resistance.海藻糖催化转变是结核分枝杆菌中的一个内在因素，它会增强表型异质性和多药耐药性。
Res Sq. 2024 Sep 13:rs.3.rs-4999164. doi: 10.21203/rs.3.rs-4999164/v1.
6
Gene Regulatory Mechanism of Mycobacterium Tuberculosis during Dormancy.结核分枝杆菌休眠期的基因调控机制
Curr Issues Mol Biol. 2024 Jun 11;46(6):5825-5844. doi: 10.3390/cimb46060348.
7
Central Metabolism Is Key Regulator of Macrophage Pyroptosis and Host Immunity.中央代谢是巨噬细胞焦亡和宿主免疫的关键调节因子。
Pathogens. 2023 Aug 30;12(9):1109. doi: 10.3390/pathogens12091109.
8
Mycobacterial phosphodiesterase Rv0805 is a virulence determinant and its cyclic nucleotide hydrolytic activity is required for propionate detoxification.分枝杆菌磷酸二酯酶 Rv0805 是一个毒力决定因子，其环核苷酸水解活性是丙酸解毒所必需的。
Mol Microbiol. 2023 Apr;119(4):401-422. doi: 10.1111/mmi.15030. Epub 2023 Mar 1.
9
One-shot C N-metabolic flux analysis for simultaneous quantification of carbon and nitrogen flux.一次 C-N 代谢通量分析用于同时定量测定碳和氮通量。
Mol Syst Biol. 2023 Mar 9;19(3):e11099. doi: 10.15252/msb.202211099. Epub 2023 Jan 27.
10
The pathogenic mechanism of Mycobacterium tuberculosis: implication for new drug development.结核分枝杆菌的致病机制：对新药研发的启示
Mol Biomed. 2022 Dec 22;3(1):48. doi: 10.1186/s43556-022-00106-y.
本文引用的文献
1
Depletion of antibiotic targets has widely varying effects on growth.抗生素靶标耗竭对生长的影响差异很大。
Proc Natl Acad Sci U S A. 2011 Mar 8;108(10):4176-81. doi: 10.1073/pnas.1018301108. Epub 2011 Feb 22.
2
Virulence of Mycobacterium tuberculosis depends on lipoamide dehydrogenase, a member of three multienzyme complexes.结核分枝杆菌的毒力取决于脂酰脱氢酶，它是三个多酶复合物的成员之一。
Cell Host Microbe. 2011 Jan 20;9(1):21-31. doi: 10.1016/j.chom.2010.12.004.
3
Simultaneous analysis of multiple Mycobacterium tuberculosis knockdown mutants in vitro and in vivo.同时在体外和体内分析多个结核分枝杆菌敲低突变体。
PLoS One. 2010 Dec 22;5(12):e15667. doi: 10.1371/journal.pone.0015667.
4
Trehalose-recycling ABC transporter LpqY-SugA-SugB-SugC is essential for virulence of Mycobacterium tuberculosis.海藻糖循环 ABC 转运蛋白 LpqY-SugA-SugB-SugC 对结核分枝杆菌的毒力至关重要。
Proc Natl Acad Sci U S A. 2010 Dec 14;107(50):21761-6. doi: 10.1073/pnas.1014642108. Epub 2010 Nov 30.
5
Carbon flux rerouting during Mycobacterium tuberculosis growth arrest.分枝杆菌生长停滞期间的碳通量重排。
Mol Microbiol. 2010 Dec;78(5):1199-215. doi: 10.1111/j.1365-2958.2010.07399.x. Epub 2010 Oct 6.
6
Metabolomics in systems microbiology.系统微生物学中的代谢组学。
Curr Opin Biotechnol. 2011 Feb;22(1):17-25. doi: 10.1016/j.copbio.2010.10.001. Epub 2010 Nov 1.
7
Metabolomics of Mycobacterium tuberculosis reveals compartmentalized co-catabolism of carbon substrates.结核分枝杆菌的代谢组学揭示了碳底物的区室化共分解代谢。
Chem Biol. 2010 Oct 29;17(10):1122-31. doi: 10.1016/j.chembiol.2010.08.009.
8
Vitamin B6 biosynthesis is essential for survival and virulence of Mycobacterium tuberculosis.维生素 B6 生物合成对于结核分枝杆菌的生存和毒力至关重要。
Mol Microbiol. 2010 Nov;78(4):980-8. doi: 10.1111/j.1365-2958.2010.07381.x. Epub 2010 Sep 22.
9
Branched tricarboxylic acid metabolism in Plasmodium falciparum.疟原虫中的支链三羧酸代谢。
Nature. 2010 Aug 5;466(7307):774-8. doi: 10.1038/nature09301.
10
Gluconeogenic carbon flow of tricarboxylic acid cycle intermediates is critical for Mycobacterium tuberculosis to establish and maintain infection.三羧酸循环中间产物的糖异生碳流对于结核分枝杆菌建立和维持感染至关重要。
Proc Natl Acad Sci U S A. 2010 May 25;107(21):9819-24. doi: 10.1073/pnas.1000715107. Epub 2010 May 3.
Zotero 插件