Rapid translational responses as a novel mechanism to repair cellular damage caused by the bacterial injectisome in animal and plant host cells

快速翻译反应作为修复动物和植物宿主细胞中细菌注射体引起的细胞损伤的新机制

• 批准号: BB/X001261/1
• 负责人: Betty Chung
• 金额: $ 77.01万
• 依托单位: University of Cambridge
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FX001261%2F1
• 关键词: Rapid; translational; responses; novel; mechanism

When animal and plant cells are assaulted by microbes, this causes changes in the production of proteins by the attacked cells. Proteins are large biological molecules with many different functions that include, among other things, structural proteins, signal molecules (including hormones), enzymes that catalyse specific chemical reactions, immune factors (including antibodies), and 'transcription factors'. Transcription factors control access to protein-making instructions archived in a cell's DNA by switching on synthesis of specific 'messenger RNA' molecules that transport copies of these instructions to 'polysomes'. Polysomes contain the complex machinery that 'translates' the data contained in each messenger RNA to guide assembly of a specific protein.Projecting from the surfaces of many disease-causing bacteria are tiny needle-like structures called 'injectisomes'. Injectisomes are nano-syringes that inject substances called 'effectors' into host cells to promote disease by, for example, inhibiting resistance. Injectisomes are used not only by bacteria that attack animals and humans, but also by bacteria that attack plants, as well as by food poisoning bacteria that colonise the edible parts of plants. Thus, understanding how cells respond to penetration by injectisomes is important for development of improved medical treatments, for enhancing protection of crops against bacterial diseases, and increasing food safety. Macrophages are white blood cells that attack invading microbes. The project leader discovered that when macrophages are penetrated by the injectisomes of attacking Salmonella bacteria, the host cell polysomes selectively increase synthesis of specific transcription factors, which in turn changes the pattern of copying of messenger RNAs from the macrophage's DNA. This reprogramming of protein synthesis activity (translation) by polysomes is remarkably rapid, occurring within seconds to minutes of penetration, and its discovery raises important new questions about how host cells respond to bacterial attack.The key questions we will answer are: - Are the polysomes of host cells responding to the effectors injected by the bacteria or to the shock of penetration? - Plant-attacking bacteria also use injectisomes are part of their armoury, so does the rapid change in polysome activity also occur when plant cells are attacked, either by bacteria that cause disease in plants, or by food poisoning bacteria that colonise plants?- How similar are the responses to bacterial and plant cells and can we separate the responses caused by the shock of penetration versus those caused by the effectors?- Is the rapid change in polysome activity an early step in mounting resistance to bacterial attack and repair of the cell, or does it mark a stage in the destruction of the host cell?

当动物和植物细胞受到微生物攻击时，这会导致受攻击细胞的蛋白质产量发生变化。蛋白质是具有许多不同功能的大生物分子，其中包括结构蛋白、信号分子（包括激素）、催化特定化学反应的酶、免疫因子（包括抗体）和“转录因子”。转录因子通过开启特定的“信使RNA”分子的合成来控制对存档在细胞DNA中的蛋白质制造指令的访问，这些分子将这些指令的拷贝运送到“多聚体”。多聚体包含复杂的机制，它可以“翻译”每个信使RNA中包含的数据，以指导特定蛋白质的组装。许多致病细菌的表面突出的是微小的针状结构，称为“注射体”。注射体是一种纳米注射器，它将称为“效应物”的物质注射到宿主细胞中，通过抑制抗性等方式促进疾病。注射体不仅被攻击动物和人类的细菌使用，而且被攻击植物的细菌使用，以及被在植物的可食用部分定植的食物中毒细菌使用。因此，了解细胞如何响应注射体的渗透对于开发改进的医学治疗，增强作物对细菌性疾病的保护以及提高食品安全性非常重要。巨噬细胞是攻击入侵微生物的白色血细胞。项目负责人发现，当巨噬细胞被攻击沙门氏菌的注射体穿透时，宿主细胞多聚核糖体选择性地增加特定转录因子的合成，这反过来改变了从巨噬细胞DNA复制信使RNA的模式。这种蛋白质合成活性的重新编程（翻译）是非常迅速的，发生在几秒钟到几分钟的渗透，它的发现提出了重要的新问题，宿主细胞如何应对细菌的攻击。我们将回答的关键问题是：-是宿主细胞的多聚核糖体响应效应器注入的细菌或冲击的渗透？- 攻击植物的细菌也使用注射体是它们军械库的一部分，那么当植物细胞受到攻击时，多核糖体活性的快速变化是否也会发生，无论是引起植物疾病的细菌，还是殖民植物的食物中毒细菌？对细菌和植物细胞的反应有多相似？我们能否将穿透冲击引起的反应与效应物引起的反应分开？多核糖体活性的快速变化是抵抗细菌攻击和修复细胞的早期步骤，还是标志着宿主细胞破坏的一个阶段？

项目成果

The distinct translational landscapes of Gram-positive and Gram-negative bacteria

革兰氏阳性菌和革兰氏阴性菌的独特翻译景观

• DOI: 10.1101/2023.05.25.542305
• 发表时间: 2023
• 作者: Bryant O

The distinct translational landscapes of gram-negative Salmonella and gram-positive Listeria.

• DOI: 10.1038/s41467-023-43759-1
• 发表时间: 2023-12-09
• 期刊: NATURE COMMUNICATIONS
• 影响因子: 16.6
• 作者: Bryant, Owain J.;Lastovka, Filip;Powell, Jessica;Chung, Betty Y. -W.
• 通讯作者: Chung, Betty Y. -W.

Pervasive translational control of photosynthesis genes during photomorphogenesis is acquired by C 4 genes

光形态发生过程中光合作用基因的普遍翻译控制是由 C 4 基因获得的

• DOI: 10.1101/2023.10.27.563924
• 发表时间: 2023
• 作者: Reyna-Llorens I

Activity of Salmonella SPI-1 inhibits the TLR4-dependent transcriptional but not translational response during macrophage infection

• DOI: 10.1101/2024.01.08.574706
• 发表时间: 2024-01
• 期刊: bioRxiv
• 作者: George Wood;Rebecca Johnson;Matthew P. Brember;Filip Lastovka;Pani Tourlomousis;Clare Bryant;B. Chung