Analysing antibacterial immunity from two sides: host versus pathogen

从宿主与病原体两个方面分析抗菌免疫

• 批准号: BB/R011834/1
• 负责人: Teresa Thurston
• 金额: $ 124.69万
• 依托单位: Imperial College London
• 依托单位国家: 英国
• 项目类别: Fellowship
• 财政年份: 2018
• 资助国家: 英国
• 起止时间: 2018 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FR011834%2F1
• 关键词: Analysing; antibacterial; immunity; two; sides

Bacterial infections represent a major problem to human health; often causing life-threatening diseases and persistent infections that can require extensive treatment with antibiotics. Salmonella causes a range of disease in humans, from gastro-enteritis to typhoid fever and is also prevalent in animals such as cattle, which can have serious economic consequences as well as public health implications. Normally, upon infection, host cells respond to bacterial products, activating a cascade of events that culminate in the production of molecules that trigger a robust immune defence programme to inactivate the bacteria. Many bacteria, including Salmonella, manipulate these host responses by the action of so-called virulence factors, producing a complex interaction between the host immune response and the incoming pathogen. This project on the one hand aims to understand how bacterial virulence factors produced and transported into host cells alter the outcome of infection to the advantage of the pathogen. We have identified several virulence factors that modulate host cell responses and we will now characterise their mechanism of action in detail. Deciphering how these virulence factors influence immune signalling cascades during infection provides valuable insight into what makes the bacteria pathogenic, provides important information on host processes that are targeted by the pathogen and is likely to provide valuable information for vaccine design and novel therapeutics. To complement this, research efforts are required to understand in molecular detail novel host mechanisms that restrict bacterial pathogens. Therefore, this project will also investigate the role of a family of host molecules (a group of proteins) that are called TRIMs. Research efforts have focused on TRIM function during viral infection but few have been studied in detail and the family remains poorly characterised during bacterial infection. Despite this, several lines of evidence suggest they have important functions upon host infection with bacteria. Therefore, I shall study how this group of proteins responds to bacterial infection and determine whether they can restrict the growth of bacteria within cells. These findings will reveal new functions for these proteins, many of which when mutated cause disease. Ultimately, with the improved understanding of host immune responses we are better informed on the best methods to combat bacterial infection. This is an important consideration given the rapidly developing rise in antibiotic resistant bacterial species.

细菌感染是人类健康的一个主要问题;经常引起危及生命的疾病和持续感染，可能需要用抗生素进行广泛治疗。沙门氏菌在人类中引起一系列疾病，从胃肠炎到伤寒，并且在牛等动物中也很流行，这可能会产生严重的经济后果以及公共卫生影响。通常，在感染后，宿主细胞对细菌产物作出反应，激活一系列事件，最终产生分子，触发强大的免疫防御程序来抵抗细菌。许多细菌，包括沙门氏菌，通过所谓的毒力因子的作用操纵这些宿主反应，在宿主免疫反应和进入的病原体之间产生复杂的相互作用。该项目一方面旨在了解细菌毒力因子如何产生并转运到宿主细胞中，从而改变感染结果，使病原体受益。我们已经确定了几个毒力因子，调节宿主细胞的反应，我们现在将详细阐述其作用机制。破译这些毒力因子如何影响感染过程中的免疫信号级联提供了有价值的见解是什么使细菌致病，提供了重要的信息，宿主过程中，病原体的目标，并可能提供有价值的信息疫苗设计和新的治疗方法。为了补充这一点，研究工作需要了解分子细节的新的宿主机制，限制细菌病原体。因此，该项目还将研究一个被称为TRIMs的宿主分子家族（一组蛋白质）的作用。研究工作集中在病毒感染期间TRIM功能，但很少有详细研究，并且在细菌感染期间该家族的特征仍然很差。尽管如此，一些证据表明它们在宿主感染细菌后具有重要功能。因此，我将研究这组蛋白质对细菌感染的反应，并确定它们是否可以限制细胞内细菌的生长。这些发现将揭示这些蛋白质的新功能，其中许多蛋白质在突变时会导致疾病。最终，随着对宿主免疫反应的进一步了解，我们可以更好地了解对抗细菌感染的最佳方法。这是一个重要的考虑因素，因为抗生素耐药性细菌物种的迅速发展。

项目成果

Interesting Biochemistries in the Structure and Function of Bacterial Effectors.

• DOI: 10.3389/fcimb.2021.608860
• 发表时间: 2021
• 期刊: Frontiers in cellular and infection microbiology
• 影响因子: 5.7
• 作者: Mak H;Thurston TLM
• 通讯作者: Thurston TLM

Speaking the host language: how Salmonella effector proteins manipulate the host.

说宿主语言：沙门氏菌效应蛋白如何操纵宿主。

• DOI: 10.1099/mic.0.001342
• 发表时间: 2023-06
• 期刊: MICROBIOLOGY-SGM
• 影响因子: 2.8
• 作者: Pillay, Timesh D.;Hettiarachchi, Sahampath U.;Gan, Jiyao;Diaz-Del-Olmo, Ines;Yu, Xiu-Jun;Muench, Janina H.;Thurston, Teresa L. M.;Pearson, Jaclyn S.
• 通讯作者: Pearson, Jaclyn S.

TIRAP in the Mechanism of Inflammation.

• DOI: 10.3389/fimmu.2021.697588
• 发表时间: 2021
• 期刊: Frontiers in immunology
• 影响因子: 7.3
• 作者: Rajpoot S;Wary KK;Ibbott R;Liu D;Saqib U;Thurston TLM;Baig MS
• 通讯作者: Baig MS