Molecular analysis of Salmonella host specificity

沙门氏菌宿主特异性的分子分析。* 我的研究计划的目的是更好地了解细菌在宿主细胞中粘附，入侵和生存的分子机制。我的研究主要集中在确定相关细菌病原体宿主特异性的遗传基础上。我们使用肠道沙门氏菌作为模型细菌，使用仅对一种宿主特异的血清型（S。伤寒），比较一个通用血清型（S。鼠伤寒沙门氏菌），可以感染许多不同的宿主。我们想知道为什么S。伤寒只针对一个宿主。*细胞表面的细菌成分，如菌毛粘附素，是第一个与周围环境相互作用的。因此，它们是负责宿主光谱的良好候选者。在下一个赠款期间，我们将集中在两个粘附系统，IV型菌毛和卷曲菌毛的表征。确定这些粘附系统在S.伤寒毒力和宿主特异性。IV型菌毛是S.伤寒及其功能尚未确定。 作为S.伤寒杆菌与宿主细胞粘附、小菌落形成、生物膜形成、抽搐运动等多种功能有关，确定其在伤寒杆菌中的作用将是最基本的。伤寒卷曲菌毛是生物膜的主要组成部分，生物膜是一种与粘附、抗性和持久性相关的细菌群落。curli基因在各血清型之间是保守的，但调控方式似乎不同，如S。伤寒在标准实验室条件下不产生卷曲和生物膜。有趣的是，S。伤寒在宿主体内产生生物膜，然后与宿主中的细菌持久性有关。无症状携带者胆结石上的生物膜是这种人类特异性病原体的唯一已知储存库。我们将确定的遗传组织，调控网络，并评估这两个粘附系统在宿主适应的作用，S。伤寒该项目将涉及使用定义的缺失突变产生突变菌株，并使用广泛的方法，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。我们将更好地了解两个重要的粘附系统的功能，在致病的细菌只适应人类。* 预计本申请中提出的研究将有助于我们理解细菌适应性，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素的作用的重要见解。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预防和治疗许多细菌的策略，无论是在宿主体内还是在环境设置中，例如在水和食物来源中。

Molecular analysis of Salmonella host specificity. ***The aim of my research program is to better understand the molecular mechanisms used by bacteria to adhere, invade and survive in host cells. My research is centred mainly on defining the genetic basis of host specificity in related bacterial pathogens. We are using Salmonella enterica as a model bacterium using a serovar that is specific only to one host (S. Typhi), in comparison to a generalist serovar (S. Typhimurium) that can infects many different hosts. We want to understand why S. Typhi is specific to only one host.***Bacterial components at the cell surface, such as fimbrial adhesins, are the first to interact with the surrounding environment. Thus, they are good candidate for being responsible of the host spectrum. During the next grant period, we will focus on the characterization of two adhesion systems, the type IV pilus and the curli fimbriae. It is important to determine the contribution of these adhesion systems in S. Typhi virulence and host specificity. The type IV pilus is unique to S. Typhi and its function is not yet identified. As the type IV pilus of S. Typhi are associated with many functions, such as attachment to host cells, microcolony, biofilm formation, and twitching motility, it will be primordial to determine its role in S. Typhi. The curli fimbriae are the main component of biofilm, a bacterial community associated with adhesion, resistance and persistence. The curli genes are conserved between the serovars, but the regulation seems to be different, as S. Typhi do not produce curli and biofilm under standard laboratory conditions. Interestingly, S. Typhi produces biofilms inside the host, and is then associated with bacterial persistence in the host. Biofilms on gallstones of asymptomatic carrier represent the only known reservoir for this human-specific pathogen.***We will determine the genetic organization, regulatory networks, and evaluate the roles of these two adhesion system in host adaptation of S. Typhi. This project will involve the generation of mutant strains using defined deletion mutations and the use of a broad range of methods including microbial genetics, molecular biology, biochemistry, immunology, cell biology, and microscopy. We will gain a better understanding of the function of two important adhesion systems in the pathogenesis of a bacteria adapted only to human. ***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 adhesins. As some of the targeted systems are conserved among other bacteria, this may potentially lead to 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.********