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

当动物和植物细胞受到微生物的攻击时，这会导致被攻击细胞产生蛋白质的变化。蛋白质是具有许多不同功能的大型生物分子，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”分子的合成来控制储存在细胞DNA中的蛋白质制造指令的获取，这些“信使RNA”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，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。从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”。注射体是纳米注射器，它将称为“效应器”的物质注射到宿主细胞中，例如通过抑制耐药性来促进疾病。注射体不仅被攻击动物和人类的细菌使用，也被攻击植物的细菌使用，以及被寄生在植物可食用部分的食物中毒细菌使用。因此，了解细胞如何对注射体的渗透作出反应，对于发展改进的医疗方法、加强对作物免受细菌性疾病的保护以及提高食品安全具有重要意义。巨噬细胞是攻击入侵微生物的白细胞。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，宿主细胞多体选择性地增加特定转录因子的合成，这反过来改变了巨噬细胞DNA中信使rna的复制模式。多聚体对蛋白质合成活性（翻译）的重编程非常迅速，在穿透后的几秒到几分钟内发生，它的发现提出了关于宿主细胞如何应对细菌攻击的重要新问题。我们将回答的关键问题是：宿主细胞的多聚体是否对细菌注入的效应器或渗透的冲击作出反应？-植物攻击细菌也使用注射体作为其武器的一部分，那么当植物细胞受到攻击时，多聚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，还是定殖在植物上的食物中毒细菌？-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器引起的反应区分开来？多聚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，还是它标志着宿主细胞破坏的一个阶段？

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?