Acquistion and selection of virulence traits of Salmonella enterica serovar Typhimurium in the organs of infected mice

感染小鼠器官中鼠伤寒沙门氏菌毒力特性的获取和选择

• 批准号: G0801161/1
• 负责人: Andrew Grant
• 金额: $ 70.22万
• 依托单位: University of Cambridge
• 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=G0801161%2F1
• 关键词: Acquistion; selection; virulence; traits; Salmonella

Salmonella enterica is a pathogen capable of causing a spectrum of diseases in humans and animals. S. enterica serovar Typhi causes approximately 22 million cases of typhoid fever and over 200,000 deaths annually; serovar Paratyphi causes about 5.5 million annual cases in humans. Other non-typhoidal Salmonella serotypes (NTS) cause gastroenteritis in humans and animals and can spread from animals to humans via contaminated food (e.g. meat and eggs). NTS are a common cause of bacteraemia and sepsis in immuno-compromised individuals (e.g. HIV and malaria patients) and in children, especially in developing countries (e.g. Africa), where they constitute a major cause of death. Current measures in the treatment of S. enterica infections have been revealed as insufficiently effective, and there is a need to develop novel vaccines and therapeutics. The interaction between S. enterica with the host immune system is complex and the outcome of the infection is the result of a fine balance between a continuous escalation of the immune response and the expression of bacterial immunoevasion mechanisms. Consequently, in order to continue growing in the tissues, S. enterica is likely to require the coordinated and sequential regulation of genes. Bacterial gene regulation has so far been investigated largely using exposure to artificial environmental conditions or to in vitro cultured cells and little information is available on how S. enterica adapts in vivo to sustain cell division and survival. Currently, it is impossible to mimic in vitro the many, possibly unknown, inflammatory events that occur during infection. Understanding how gene regulation affects virulence traits of bacterial pathogens in vivo is one of the major challenges of the post-genomic era. Using microbiology, microscopy and sensitive molecular techniques we aim to develop an understanding of the dynamic interactions between host and bacterial mechanisms that determine net growth rates of S. enterica within the host. These experiments will help us to develop an understanding of the influence of passage in a host on the fitness and virulence of S. enterica, which will directly inform the development of novel vaccines and strategies to control and treat a major global health problem.

肠沙门氏菌是一种能够引起人类和动物一系列疾病的病原体。伤寒沙门氏菌每年导致约 2200 万例伤寒病例和超过 20 万人死亡；副伤寒血清型每年在人类中引起约 550 万例病例。其他非伤寒沙门氏菌血清型 (NTS) 会引起人类和动物胃肠炎，并可通过受污染的食物（例如肉和蛋）从动物传播给人类。 NTS 是免疫功能低下个体（例如艾滋病毒和疟疾患者）和儿童中菌血症和败血症的常见原因，特别是在发展中国家（例如非洲），它们是导致死亡的主要原因。目前治疗肠沙门氏菌感染的措施已被证明不够有效，需要开发新的疫苗和治疗方法。肠沙门氏菌与宿主免疫系统之间的相互作用是复杂的，感染的结果是免疫反应持续升级和细菌免疫逃避机制表达之间良好平衡的结果。因此，为了在组织中继续生长，肠沙门氏菌可能需要基因的协调和顺序调控。迄今为止，细菌基因调控的研究主要是通过暴露于人工环境条件或体外培养细胞来进行的，而关于肠沙门氏菌如何在体内适应以维持细胞分裂和存活的信息很少。目前，不可能在体外模拟感染过程中发生的许多可能未知的炎症事件。了解基因调控如何影响体内细菌病原体的毒力特征是后基因组时代的主要挑战之一。利用微生物学、显微镜和敏感分子技术，我们的目标是了解宿主和细菌机制之间的动态相互作用，这些机制决定了宿主内肠沙门氏菌的净生长速率。这些实验将帮助我们了解宿主传代对肠沙门氏菌的适应性和毒力的影响，这将直接为新型疫苗的开发以及控制和治疗全球主要健康问题的策略提供信息。