A novel mechanism of translational regulation in bacteria: de-repression of non-canonical start codons in response to oxidative stress

细菌翻译调控的新机制：响应氧化应激而解除非规范起始密码子的抑制

• 批准号: BB/L019825/1
• 负责人: Mark Buttner
• 金额: $ 59.94万
• 依托单位: John Innes Centre
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2014
• 资助国家: 英国
• 起止时间: 2014 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FL019825%2F1
• 关键词: novel; mechanism; translational; regulation; bacteria

The harmless soil bacteria called streptomycetes are vital to human welfare because they are the source of the vast majority of antibiotics used by doctors to cure infectious diseases, as well as providing us with numerous other medicines used, for example, to treat cancer, and to help organ transplant patients. We have identified a master regulator (called a 'transcription factor') that switches the genetic machinery of these useful bacteria to allow them to survive in the presence of toxic molecules called Reactive Oxygen Species (a condition called "oxidative stress"). The aim of this work is to find out exactly how the activity of this master regulator is controlled at the molecular level. We also know that this same master regulator controls resistance to oxidative stress in the pathogens Mycobacterium tuberculosis and Corynebacterium diphtheriae, the bacteria that cause the fatal diseases tuberculosis and diphtheria, respectively. This is important because white blood cells ingest pathogenic bacteria and expose them to Reactive Oxygen Species in order to kill them, and so the mechanisms by which disease-causing bacteria like M. tuberculosis and C. diphtheriae resist this oxidative killing are potentially important to human health.

被称为链霉菌的无害土壤细菌对人类福祉至关重要，因为它们是医生用来治疗传染病的绝大多数抗生素的来源，以及为我们提供许多其他药物的来源，例如，治疗癌症和帮助器官移植患者。我们已经确定了一种主调控因子(称为‘转录因子’)，它可以切换这些有用细菌的遗传机制，使它们能够在名为活性氧种(一种称为“氧化应激”的情况)的有毒分子存在的情况下生存。这项工作的目的是确切地找出这个主调控因子的活性是如何在分子水平上被控制的。我们还知道，同样的主调控子控制着病原体结核分枝杆菌和白喉棒状杆菌对氧化应激的抵抗力，这两种细菌分别导致致命的结核病和白喉。这一点很重要，因为白细胞会吞噬致病细菌，并将它们暴露在活性氧物种中以杀死它们，因此结核分枝杆菌和白喉杆菌等致病细菌抵抗这种氧化杀灭的机制对人类健康具有潜在的重要意义。

项目成果

Translational Control of the SigR-Directed Oxidative Stress Response in Streptomyces via IF3-Mediated Repression of a Noncanonical GTC Start Codon.

• DOI: 10.1128/mbio.00815-17
• 发表时间: 2017-06-13
• 期刊: mBio
• 影响因子: 6.4
• 作者: Feeney MA;Chandra G;Findlay KC;Paget MSB;Buttner MJ
• 通讯作者: Buttner MJ

Two dynamin-like proteins stabilize FtsZ rings during Streptomyces sporulation

• DOI: 10.1073/pnas.1704612114
• 发表时间: 2017-07-25
• 期刊: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• 影响因子: 11.1
• 作者: Schlimpert, Susan;Wasserstrom, Sebastian;Buttner, Mark J.
• 通讯作者: Buttner, Mark J.

Genome-Wide Chromatin Immunoprecipitation Sequencing Analysis Shows that WhiB Is a Transcription Factor That Cocontrols Its Regulon with WhiA To Initiate Developmental Cell Division in Streptomyces.

• DOI: 10.1128/mbio.00523-16
• 发表时间: 2016-04-19
• 期刊: mBio
• 影响因子: 6.4
• 作者: Bush MJ;Chandra G;Bibb MJ;Findlay KC;Buttner MJ
• 通讯作者: Buttner MJ

Fluorescence Time-lapse Imaging of the Complete S. venezuelae Life Cycle Using a Microfluidic Device.

• DOI: 10.3791/53863
• 发表时间: 2016-02-28
• 期刊: Journal of visualized experiments : JoVE
• 作者: Schlimpert S;Flärdh K;Buttner J
• 通讯作者: Buttner J