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A metabolomics approach exploring the function of the ESX-3 type VII secretion system of M. smegmatis

机译:代谢组学方法探索耻垢分枝杆菌ESX-3 VII型分泌系统的功能

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摘要

The genome of Mycobacterium, including Mycobacterium tuberculosis, contains five copies of a cluster of genes encoding a novel type VII secretion system, named the ESX gene cluster region. This ESX-3 gene cluster is essential for in vitro growth and is thought to play a role in iron and zinc homeostasis, however, its exact functionality remains an enigma. A metabolomics research approach was subsequently used to compare the metabolite profiles of a M. smegmatis ESX-3 knockout strain to that a wild type parental strain, in order to elucidate its functionality from a metabolic perspective. Statistical analysis of the GC–MS generated data showed a clear separation between the wild type and knockout sample groups, based on the analysed metabolite profiles of these organisms. Of all the metabolite markers identified, various amino acids and metabolite pathways related to these, appeared to be most affected by the ESX-3 knockout, especially those with enzymes regulated by iron and zinc, supporting previous genomics and proteomics generated hypotheses and findings. This study is the first to demonstrate the capacity of using metabolomics, in conjunction with previous genomics and proteomic findings, to identify underlying metabolic changes and confirm previous hypotheses related to the functionality of ESX-3 in Mycobacterium growth and survival.
机译:包括结核分枝杆菌在内的分枝杆菌的基因组包含五个拷贝的基因簇的副本,这些基因簇编码一种名为VII的新型VII分泌系统。 ESX-3基因簇对于体外生长至关重要,被认为在铁和锌稳态中起作用,但是,其确切功能仍是一个谜。随后使用了代谢组学研究方法来比较耻垢分枝杆菌ESX-3基因敲除菌株与野生型亲本菌株的代谢产物概况,以便从代谢角度阐明其功能。对GC-MS生成数据的统计分析表明,根据分析后的有机物代谢物谱,野生型和基因敲除样品组之间存在明显的分离。在鉴定出的所有代谢物标记物中,与氨基酸相关的各种氨基酸和代谢物途径似乎受ESX-3基因敲除的影响最大,尤其是那些受铁和锌调节的酶,从而支持先前的基因组学和蛋白质组学产生的假设和发现。这项研究首次证明了利用代谢组学与先前的基因组学和蛋白质组学发现相结合的能力,以识别潜在的代谢变化并确认与ESX-3在分枝杆菌生长和存活中的功能有关的先前假设。

著录项

  • 来源
    《Metabolomics》 |2013年第3期|631-641|共11页
  • 作者单位

    School for Physical and Chemical Sciences Centre for Human Metabonomics North-West University">(1);

    School for Physical and Chemical Sciences Centre for Human Metabonomics North-West University">(1);

    DST/NRF Centre of Excellence in Biomedical Tuberculosis Research US/MRC Centre for Molecular and Cellular Biology Division of Molecular Biology and Human Genetics Department of Biomedical Sciences Faculty of Health Sciences Stellenbosch University">(2);

    DST/NRF Centre of Excellence in Biomedical Tuberculosis Research US/MRC Centre for Molecular and Cellular Biology Division of Molecular Biology and Human Genetics Department of Biomedical Sciences Faculty of Health Sciences Stellenbosch University">(2);

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    Metabolomics; ESX-3 knockout; Iron and zinc homeostasis; Amino acid metabolism;

    机译:代谢组学ESX-3淘汰赛;铁和锌的动态平衡;氨基酸代谢;

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