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

肠道沙门氏菌是一种能够在人类和动物中引起一系列疾病的病原体。S.伤寒血清型每年引起大约2200万例伤寒和超过200，000例死亡;副伤寒血清型每年引起大约550万例人类病例。其他非伤寒沙门氏菌血清型（NTS）可引起人类和动物的胃肠炎，并可通过受污染的食物（如肉类和蛋类）从动物传播给人类。NTS是免疫功能低下个体（例如HIV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），它们构成死亡的主要原因。目前对S.肠道感染已被揭示为不够有效，因此需要开发新的疫苗和治疗剂。S.肠道感染与宿主免疫系统的关系是复杂的，并且感染的结果是免疫应答的持续升级和细菌免疫逃避机制的表达之间的良好平衡的结果。因此，为了在组织中继续生长，S.肠道菌可能需要基因的协调和顺序调节。迄今为止，细菌基因调控主要是通过暴露于人工环境条件或体外培养细胞来研究的，关于S。肠道适应在体内维持细胞分裂和生存。目前，在体外模拟感染过程中发生的许多可能未知的炎症事件是不可能的。了解基因调控如何影响体内细菌病原体的毒力性状是后基因组时代的主要挑战之一。利用微生物学，显微镜和敏感的分子技术，我们的目标是发展宿主和细菌之间的动态相互作用的机制，决定净增长率的理解。肠道内的宿主。这些实验将有助于我们了解在宿主中传代对沙门氏菌适应性和毒力的影响。Enterica，它将直接为新型疫苗和控制和治疗全球重大健康问题的策略的开发提供信息。

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.