Copper resistance in salmonella

沙门氏菌的铜抗性

• 批准号: BB/G010765/1
• 负责人: Jennifer Cavet
• 金额: $ 49.3万
• 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: 2009
• 资助国家: 英国
• 起止时间: 2009 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FG010765%2F1
• 关键词: Copper; resistance; salmonella

Food-borne Salmonella infections cause serious medical and veterinary problems worldwide. In the developed world, salmonellosis continues to be one of the most common forms of food-poisoning and mainly occurs due to the consumption of contaminated animal products. Salmonella food poisoning represents a serious health risk and is usually characterised by the acute onset of fever, abdominal pain, diarrhea, nausea and occasionally vomiting but in some cases the disease can become more severe and life-threatening. Following oral ingestion of Salmonella, disease is started by the bacteria being able to survive within the intestinal tract and invade intestinal cells. The ability of the bacteria to reside in host immune cells (macrophages) is important for their spread to different organs and systemic disease. Survival within the different locations of the host requires that Salmonella can sense and adapt to changing environmental conditions such as varying metal levels. One such metal is copper. Copper is required by Salmonella for several key enzymes but is also extremely toxic. Our preliminary studies have now indicated that resistance to copper-stress plays a vital role during Salmonella infections. This project aims to build upon these studies and provide a detailed characterisation of the mechanisms of copper-resistance in this pathogen and their roles during infection. Furthermore, we will test the hypothesis that copper transporters in host cells contribute to their ability to kill bacteria by supplying copper to generate highly toxic reactive oxygen species. Understanding the environmental challenges that occur in the infected host and the mechanisms which protect Salmonella from copper stress may help in developing novel therapeutics to combat disease. Furthermore, there is a growing use of copper as a means of controlling bacterial growth in agriculture and the food industry. Clearly this has implications for the development of more resistant bacteria. Hence, a thorough understanding of the copper-resistance systems in Salmonella and their role in virulence is vital.

食源性沙门氏菌感染在全世界范围内造成严重的医疗和兽医问题。在发达国家，沙门氏菌病仍然是最常见的食物中毒形式之一，主要是由于食用受污染的动物产品而发生的。沙门氏菌食物中毒会带来严重的健康风险，通常表现为急性发热、腹痛、腹泻、恶心，偶尔呕吐，但在某些情况下，疾病可能会变得更加严重并危及生命。口服摄入沙门氏菌后，细菌能够在肠道内存活并侵入肠道细胞，从而引发疾病。细菌驻留在宿主免疫细胞（巨噬细胞）中的能力对于它们传播到不同器官和全身性疾病很重要。在宿主的不同位置生存需要沙门氏菌能够感知并适应不断变化的环境条件，例如不同的金属水平。其中一种金属是铜。沙门氏菌的几种关键酶需要铜，但铜也具有剧毒。我们的初步研究现已表明，对铜应激的抵抗力在沙门氏菌感染过程中起着至关重要的作用。该项目旨在以这些研究为基础，详细描述该病原体的铜抗性机制及其在感染过程中的作用。此外，我们将检验这样的假设：宿主细胞中的铜转运蛋白通过提供铜产生剧毒的活性氧来增强其杀死细菌的能力。了解受感染宿主中发生的环境挑战以及保护沙门氏菌免受铜应激的机制可能有助于开发新的疗法来对抗疾病。此外，越来越多地使用铜作为农业和食品工业中控制细菌生长的手段。显然，这对耐药细菌的发展具有重要意义。因此，彻底了解沙门氏菌的铜抗性系统及其在毒力中的作用至关重要。

项目成果

Atypical copper homeostasis in Salmonella Typhimurium

鼠伤寒沙门氏菌的非典型铜稳态

• 作者: Jennifer Cavet (Principle Investigator)

Copper homeostasis and Salmonella pathogenicity

铜稳态和沙门氏菌致病性

• 作者: Jennifer Cavet (Author)

Copper homeostasis in Salmonella is atypical and copper-CueP is a major periplasmic metal complex.

• DOI: 10.1074/jbc.m110.145953
• 发表时间: 2010-08-13
• 期刊: The Journal of biological chemistry
• 作者: Osman D;Waldron KJ;Denton H;Taylor CM;Grant AJ;Mastroeni P;Robinson NJ;Cavet JS
• 通讯作者: Cavet JS