Food-borne Listeria infections: Zinc homeostasis at the host-pathogen interface

食源性李斯特菌感染：宿主-病原体界面的锌稳态

• 批准号: BB/K016881/1
• 负责人: Jennifer Cavet
• 金额: $ 49.26万
• 依托单位: University of Manchester
• 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%2FK016881%2F1
• 关键词: Food; borne; Listeria; infections; Zinc

The bacterium Listeria monocytogenes causes serious food-borne disease in man, with high mortality rates despite antibiotic intervention. The disease can range from stillbirth in infected women, septicaemia (blood poisoning) and meningitis. People with weakened immune systems are particularly susceptible to this disease. A feature of Listeria is its ability to survive a range of harsh conditions and grow at low temperatures routinely used to store food. In order for Listeria to grow, it must acquire the metal zinc. This is true not only during life in the environment, on food and food preparation surfaces, but also during infection of a host. This proposal aims to understand how Listeria acquires zinc especially in conditions inside the host where available zinc may be in short supply. We have already identified two zinc-uptake systems and shown that these are vital for Listeria to be able to survive when there is very little zinc available and also for it to be able to cause infections. Having discovered these systems, the next step is to gain a more detailed understanding of how each one contributes to obtaining zinc and their roles during Listeria infections. We will also seek to find other systems that are needed by Listeria to handle zinc. An important impact of understanding the mechanisms by which Listeria acquires zinc and controls its zinc levels will be the opportunity to exploit this knowledge to design new ways of combating Listeria infections and design new control strategies to reduce contamination of foods by Listeria.

单核细胞增生李斯特菌会导致人类严重的食源性疾病，尽管有抗生素干预，死亡率仍很高。这种疾病的范围包括受感染妇女的死产、败血症（血液中毒）和脑膜炎。免疫系统较弱的人特别容易患上这种疾病。李斯特菌的一个特征是它能够在一系列恶劣条件下生存，并在通常用于储存食物的低温下生长。为了使李斯特菌生长，它必须获得金属锌。这不仅在环境中、食物和食物制备表面上的生活中是如此，而且在宿主感染期间也是如此。该提案旨在了解李斯特菌如何获得锌，特别是在宿主体内可用锌可能短缺的条件下。我们已经确定了两个锌吸收系统，并表明这些系统对于李斯特菌在锌含量很少的情况下能够存活以及能够引起感染至关重要。发现这些系统后，下一步是更详细地了解每个系统如何有助于获得锌及其在李斯特菌感染期间的作用。我们还将寻求李斯特菌处理锌所需的其他系统。了解李斯特菌获得锌和控制其锌水平的机制的重要影响将是利用这些知识来设计对抗李斯特菌感染的新方法和设计新的控制策略以减少李斯特菌对食品的污染的机会。

项目成果

RNA-based thermoregulation of a Campylobacter jejuni zinc resistance determinant.

• DOI: 10.1371/journal.ppat.1009008
• 发表时间: 2020-10
• 期刊: PLoS pathogens
• 影响因子: 6.7
• 作者: Barnawi H;Masri N;Hussain N;Al-Lawati B;Mayasari E;Gulbicka A;Jervis AJ;Huang MH;Cavet JS;Linton D
• 通讯作者: Linton D

Trace Metals and Infectious Diseases

微量金属与传染病

• 发表时间: 2015
• 作者: Cavet JS

Structure-Based Design of MptpB Inhibitors That Reduce Multidrug-Resistant Mycobacterium tuberculosis Survival and Infection Burden in Vivo.

• DOI: 10.1021/acs.jmedchem.8b00832
• 发表时间: 2018-09-27
• 期刊: Journal of medicinal chemistry
• 影响因子: 7.3
• 作者: Vickers CF;Silva APG;Chakraborty A;Fernandez P;Kurepina N;Saville C;Naranjo Y;Pons M;Schnettger LS;Gutierrez MG;Park S;Kreiswith BN;Perlin DS;Thomas EJ;Cavet JS;Tabernero L
• 通讯作者: Tabernero L

Battling against nutritional immunity: Bacterial systems for avoiding zinc and copper stress

对抗营养免疫：避免锌和铜应激的细菌系统

• 发表时间: 2016
• 作者: Cavet JS