Molecular analysis of Salmonella host specificity

该研究计划的目的是确定具有不同宿主范围的相关细菌中宿主特异性的遗传基础。我们的模型细菌是伤寒沙门氏菌（S.伤寒），这是主机限制（具体到只有一个主机）相比，充分研究的S。肠道血清型鼠伤寒沙门氏菌可感染许多动物物种。细菌细胞被膜成分是最先与周围环境相互作用的。因此，我们正在研究粘附系统和铁获取系统，以了解细菌适应和进化的基本方面。我们的目标是：1）表征S。Typhi粘附系统（2）确定和表征铁稳态的调节网络;（3）表征和确定铁获取系统在宿主适应中的作用。这些研究将采用新开发的全球基因表达的分子遗传学工具，将涉及突变菌株的产生和广泛的方法，包括微生物遗传学，分子生物学，生物化学，免疫学，细胞生物学和显微镜的使用。多方面的培训环境将向学员介绍学科的多样性，这将是他们发展的重要资产，应导致在生物和自然科学方面取得成功的职业生涯。预计本申请中提出的研究将有助于我们了解细菌适应性，适应性和进化的基本机制。这些信息也应该提供关于细菌粘附和铁稳态的作用的重要见解。由于一些靶向系统在其他细菌中是保守的，这可能会导致在不同环境中，在宿主和环境设置中，例如在水和食物来源中，针对许多细菌的预防和治疗的共同策略。

The aim of this research program focuses on defining the genetic basis of host-specificity in related bacteria with different host ranges. Our model bacterium is Salmonella enterica serovar Typhi (S. Typhi), which is host-resctricted (specific to only one host) in comparison to the well-studied S. enterica serovar Typhimurium that can infect many animal species. Bacterial cell envelope components are the first to interact with the surrounding environment. We are therefore investigating adhesion systems and iron-acquisition systems to understand fundamental aspects of bacterial adaptation and evolution. Our objectives will be to: 1) characterize S. Typhi adhesion systems; (2) identify and characterize the regulatory network of iron homeostasis and (3) to characterize and determine roles of iron-acquisition systems in host adaptation. These studies will employ newly developed molecular genetic tools for global gene expression, will involve the generation of mutant strains and the use of a broad range of methods including microbial genetics, molecular biology, biochemistry, immunology, cell biology, and microscopy. The multifaceted training environment will introduce trainees to a diversity of disciplines that will be an important asset for their development that should lead to successful careers in biological and natural sciences.It is anticipated that the research proposed in this application will contribute to our understanding of basic mechanisms of bacterial fitness, adaptation and evolution. This information should also provide important insights regarding the roles of bacterial adhesion and iron homeostasis. As some of the targeted systems are conserved among other bacteria, this may potentially lead to common strategies for prevention and treatment against many bacteria in different environments, both within the host and in environmental settings, such as in water and food sources.