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

单核细胞增生李斯特菌在人类中引起严重的食源性疾病，尽管有抗生素干预，但死亡率很高。这种疾病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这种疾病。李斯特菌的一个特点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。不仅在生活环境中，在食物和食物制备表面，而且在感染宿主期间也是如此。本研究旨在了解李斯特菌是如何获取锌的，特别是在宿主体内锌供应不足的情况下。我们已经确定了两种锌摄取系统，并表明它们对于李斯特菌在锌非常少的情况下能够存活以及能够引起感染至关重要。在发现了这些系统之后，下一步就是更详细地了解每个系统是如何帮助获得锌的，以及它们在李斯特菌感染期间的作用。我们还将寻找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一个重要影响将是利用这一知识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。

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.