Copper Homeostasis and virulence in Listeria monocytogenes

单核细胞增生李斯特菌的铜稳态和毒力

• 批准号: G0601205/1
• 负责人: Ian Roberts
• 金额: $ 66.56万
• 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: 2007
• 资助国家: 英国
• 起止时间: 2007 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0601205%2F1
• 关键词: Copper; Homeostasis; virulence; Listeria; monocytogenes

Listeria monocytogenes is a food borne bacterium that causes a number of serious infections in humans. Infection may be of the unborn/newly born infant where disease may manifest as listeric abortion, stillbirth or late-onset neonatal listeriosis. In adults, infection usually affects the central nervous system causing meningitis. In the USA L. monocytogenes accounts for 28% of all fatalities as a consequence of food borne infection and in cancer patients, L. monocytogenes is the most commonly encountered form of bacterial meningitis. The aims of this project are to understand copper homeostasis in L. monocytogenes and to establish its importance in infection.In order to survive bacteria have to be able to adapt to changes in their local environment and maintain homeostasis. The ability to respond to changes in the levels of transition elements such as copper provides a dilemma. Bacteria have to balance how to obtain sufficient copper, an essential cofactor for certain enzymes, with the toxicity of copper to the cell. In L. monocytogenes the problem of copper homeostasis is particularly acute. It inhabits environments including soil, effluents and food where it will be exposed to fluctuating copper levels. The use of copper as an anti-microbial in animal feeds, as a disinfectant in factory-based farming and as a biocide in fruit production means L. monocytogenes will have to combat potentially toxic levels of copper during food production and processing. Adapting to fluctuations in the level of copper is important during infections. L. monocytogenes replicates in a number of host tissues that will offer different challenges with regard to copper availability. Early in infection L. monocytogenes grows in the gall bladder, where there are high levels of copper. In contrast, in the liver and spleen it replicates in an environment containing little free copper and where the acquisition of sufficient copper for growth is essential. Adapting to these different niches within the host offers a challenge for a successful infection. In terms of improvements to human health, there are a number of potential benefits. First, an understanding copper homeostasis in this important food borne pathogen will inform the current copper based treatments used in food production and lead to effective regimes to reduce L. monocytogenes contamination. Secondly by establishing the essential role for copper homeostasis in infection it may be possible in the longer term to develop novel non-antibiotic based approaches for treatment of infections based on disruption of copper homeostasis.

单核细胞增生李斯特菌是一种食源性细菌，可导致人类严重感染。感染可能发生在未出生/新生儿身上，其疾病可能表现为流产、死产或迟发性新生儿败血症。在成年人中，感染通常会影响中枢神经系统，导致脑膜炎。在美国L.单核细胞增生李斯特菌占所有死亡的28%，由于食物传播的感染和癌症患者，单核细胞增多症是细菌性脑膜炎最常见的形式。本研究的目的是了解L.为了生存，细菌必须能够适应其局部环境的变化并保持体内平衡。对过渡元素如铜的水平变化的响应能力提供了一个困境。细菌必须平衡如何获得足够的铜，某些酶的必要辅因子，以及铜对细胞的毒性。在洛单核细胞增多症铜体内平衡的问题特别严重。它栖息的环境包括土壤，污水和食物，它将暴露于波动的铜水平。铜在动物饲料中用作抗菌剂，在工厂化养殖中用作消毒剂，在水果生产中用作杀生物剂，意味着L。在食品生产和加工过程中，单核细胞增多症患者将不得不与潜在的有毒铜水平作斗争。在感染期间，适应铜水平的波动很重要。L.单核细胞增多症在许多宿主组织中复制，这将对铜的可用性提出不同的挑战。感染早期L.单核细胞增多症生长在胆囊中，那里有高水平的铜。相反，在肝脏和脾脏中，它在含有少量游离铜的环境中复制，并且在那里获得足够的铜用于生长是必不可少的。适应宿主体内这些不同的小生境为成功感染提供了挑战。在改善人类健康方面，有许多潜在的好处。首先，了解这种重要的食源性病原体中的铜稳态将为目前用于食品生产的基于铜的治疗提供信息，并导致有效的治疗方案，以减少L。单核细胞增多症其次，通过建立铜稳态在感染中的重要作用，从长远来看，有可能开发基于铜稳态破坏的新型非抗生素治疗感染的方法。