Copper resistance in salmonella

食源性沙门氏菌感染在世界范围内引起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。沙门氏菌食物中毒是一种严重的健康风险，通常表现为急性发热，腹痛，腹泻，恶心和偶尔呕吐，但在某些情况下，这种疾病可能会变得更加严重并危及生命。在口服沙门氏菌后，疾病是由能够在肠道内存活并侵入肠细胞的细菌开始的。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非常重要。在宿主的不同位置内生存需要沙门氏菌能够感知和适应不断变化的环境条件，例如不同的金属水平。一种这样的金属是铜。铜是沙门氏菌几种关键酶所必需的，但也具有极强的毒性。我们的初步研究表明，对铜胁迫的抵抗在沙门氏菌感染中起着至关重要的作用。该项目旨在建立在这些研究的基础上，并提供了一个详细的特点，在这种病原体的耐铜性的机制和它们在感染过程中的作用。此外，我们将测试的假设，在宿主细胞中的铜转运蛋白有助于他们的能力，通过提供铜，产生高毒性的活性氧杀死细菌。了解感染宿主中发生的环境挑战以及保护沙门氏菌免受铜胁迫的机制可能有助于开发新的治疗方法来对抗疾病。此外，在农业和食品工业中，越来越多地使用铜作为控制细菌生长的手段。显然，这对开发更具耐药性的细菌有影响。因此，彻底了解沙门氏菌中的铜抗性系统及其在毒力中的作用至关重要。

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.