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Breaking the walls to wake-up bacterial cells

打破墙壁唤醒细菌细胞

基本信息

批准号：
BB/H008586/1
负责人：
Galina Mukamolova
金额：
$ 40.13万
依托单位：
University of Leicester
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2010
资助国家：
英国
起止时间：
2010 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=BB%2FH008586%2F1
关键词：
Breaking walls wake up bacterial

项目摘要

Bacteria can survive harsh environmental conditions by slowing down their major living processes. They look like normal cells but behave like the dead ones until stimulated by proteins called the Resuscitation-promoting factors (Rpfs). Rpfs are constantly sectereted by normal growing bacteria and play an important role in making of cell envelope. However, sleeping or dormant bacteria do not produce the Rpfs. The main goal of this project is to find out how Rpfs wake-up sleeping cells. Rpfs are enzymes which digest bacterial cell wall (like lyzosyme) but unlike the latter they don't kill cells and somehow modify their envelope. Rpfs may simply break quite inflexible cell wall of sleeping cells and make them 'free' to grow and expand. In more sophisticated model fragments of cell wall, released by Rpfs during digestion, have a very special function as signalling molecules. In other words they are waking-up messages for dormant cells. These 'signals' bind to other molecules on the bacterial surface and initiate a complex system called a protein kinase cascade, a well described mechanisms of cell regulation in multicellular organisms. To address both hypotheses the investigator will isolate the major part of bacterial envelope, called murein and digest it with different Rpfs. The resulting products will be used for resuscitation of dormant cells and their composition will be analysed and characterised. Other experiments will be designed to establish what bonds the Rpfs cut in murein and how this cleavage influences the structure of bacterial cell envelope. In separate part of the project the investigators will attempt to understand how bacterial cells control the enzymes which able to destroy them by 'eating' bacterial envelope. Rpfs proteins will be applied as an example of such cell-wall degrading enzymes. The results of the project will not only satisfy scientific curiosity on bacterial cell function but also provide novel methods for manipulating of physiological condition of bacteria and further improving their application in biotechnology, medicine and specifically for combating of persisting infections caused by dormant bacteria.

细菌可以通过减缓其主要的生活过程在恶劣的环境条件下生存。它们看起来像正常细胞，但在被一种叫做复苏促进因子（Rpfs）的蛋白质刺激之前，它们的行为就像死去的细胞一样。Rpfs由正常生长的细菌不断分泌，在细胞包膜的形成中起重要作用。然而，睡眠或休眠的细菌不产生Rpfs。该项目的主要目标是找出Rpfs是如何唤醒睡眠细胞的。Rpfs是一种消化细菌细胞壁的酶（如溶溶酶），但与溶溶酶不同的是，它们不杀死细胞，而是以某种方式修饰细胞的包膜。Rpfs可能只是简单地打破睡眠细胞相当僵硬的细胞壁，使它们“自由”地生长和扩张。在更复杂的模型中，Rpfs在消化过程中释放的细胞壁碎片作为信号分子具有非常特殊的功能。换句话说，它们是唤醒休眠细胞的信息。这些“信号”与细菌表面的其他分子结合，并启动一个称为蛋白激酶级联的复杂系统，这是多细胞生物中细胞调节的一种很好的机制。为了解决这两种假设，研究者将分离细菌包膜的主要部分，称为murin，并用不同的Rpfs消化它。所产生的产品将用于休眠细胞的复苏，其成分将被分析和表征。其他的实验将被设计来确定Rpfs在小鼠中切割什么键，以及这种切割如何影响细菌细胞包膜的结构。在该项目的另一部分，研究人员将试图了解细菌细胞如何通过“吃掉”细菌包膜来控制能够摧毁它们的酶。Rpfs蛋白将作为这种细胞壁降解酶的一个例子。该项目的研究成果不仅将满足人们对细菌细胞功能的科学好奇心，而且将为控制细菌的生理状态提供新的方法，进一步提高其在生物技术、医学上的应用，特别是在对抗休眠细菌引起的持续感染方面的应用。

项目成果

期刊论文数量（10）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Efficient Protein Digestion at Elevated Temperature in the Presence of Sodium Dodecyl Sulfate and Calcium Ions for Membrane Proteomics.

在十二烷基硫酸钠和钙离子存在下，在高温下高效消化蛋白质，用于膜蛋白质组学。

DOI：
10.1021/acs.analchem.9b00484
发表时间：
2019
期刊：
Analytical chemistry
影响因子：
7.4
作者：
Loraine J
通讯作者：
Loraine J

Antimicrobial treatment improves mycobacterial survival in nonpermissive growth conditions.

DOI：
10.1128/aac.02774-13
发表时间：
2014-05
期刊：
Antimicrobial agents and chemotherapy
影响因子：
4.9
作者：
Turapov O;Waddell SJ;Burke B;Glenn S;Sarybaeva AA;Tudo G;Labesse G;Young DI;Young M;Andrew PW;Butcher PD;Cohen-Gonsaud M;Mukamolova GV
通讯作者：
Mukamolova GV

Oleoyl coenzyme A regulates interaction of transcriptional regulator RaaS (Rv1219c) with DNA in mycobacteria.

DOI：
10.1074/jbc.m114.577338
发表时间：
2014-09-05
期刊：
The Journal of biological chemistry
影响因子：
0
作者：
Turapov O;Waddell SJ;Burke B;Glenn S;Sarybaeva AA;Tudo G;Labesse G;Young DI;Young M;Andrew PW;Butcher PD;Cohen-Gonsaud M;Mukamolova GV
通讯作者：
Mukamolova GV

Phenotypically Adapted Mycobacterium tuberculosis Populations from Sputum Are Tolerant to First-Line Drugs.

DOI：
10.1128/aac.01380-15
发表时间：
2016-04
期刊：
Antimicrobial agents and chemotherapy
影响因子：
4.9
作者：
Turapov O;O'Connor BD;Sarybaeva AA;Williams C;Patel H;Kadyrov AS;Sarybaev AS;Woltmann G;Barer MR;Mukamolova GV
通讯作者：
Mukamolova GV

Development of an In Vitro Assay for Detection of Drug-Induced Resuscitation-Promoting-Factor-Dependent Mycobacteria.