Analysis of Virulence factors in understudied Salmonella serovars

在这个项目中，我们将在细胞和动物感染模型中研究沙门氏菌，我们将使用分子生物学，显微镜和生物化学技术的组合来了解沙门氏菌血清型感染如何导致不同的表现。沙门氏菌属含有人类和动物的几种重要病原体，是全球食源性疾病的最大贡献者之一。该属只有2个种：S. bongori和S.肠的。然而，S.肠杆菌包含6个亚种和超过2000个血清型，根据不同的表面抗原进行表征。重要的是，不同的血清型是导致非常不同的疾病与一些，如沙门氏菌伤寒（S。伤寒沙门氏菌（S.副伤寒沙门氏菌（Paratyphi），又称“伤寒沙门氏菌（Typhoidal Salmonella）”，在人类中引起全身性的、威胁生命的疾病，而其他沙门氏菌（非伤寒沙门氏菌）感染一系列宿主并引起轻度的、自限性的胃肠炎，在免疫功能低下的宿主中可能变得严重。伤寒，因为它对人类健康至关重要，和S。鼠伤寒是人类和动物中最常见的一种。然而，由于临床和环境样本基因组测序的急剧增加，现有的信息已经挑战了一些基于伤寒/鼠伤寒比较的“教条”。例如，最初被描述为S.伤寒特异性毒素也由其他47种非伤寒血清型表达。这一发现推动了对以前公认的模型的修订，并刺激了大量关于毒素作用及其生物学的新研究。此外，丰富的基因组数据使我们能够以良好的置信度研究不同血清型中某些毒力因子之间的关系。事实上，我们有初步的数据表明，收购的毒力因子并不一定会导致增加的毒力，其中一些是功能上不兼容，我们认为，疾病类型（系统性或自限性）和严重程度是由一组毒力因子“挑选”在某个血清型的演变过程中。

In this project we will study Salmonella in both cellular and animal infection models and we will use a mix of molecular biology, microscopy and biochemistry techniques to understand how Salmonella serovars infection can result in different manifestations. The genus Salmonella contains several important pathogens for humans and animals and is one of the largest contributors of food borne illness worldwide. The genus comprises only 2 species: S. bongori and S. enterica. However, S. enterica contains 6 subspecies and more than ~2000 serovars characterised according to different surface antigens. Importantly, different serovars are responsible for causing very different diseases with some, such as Salmonella enterica Typhi (S. Typhi) and Salmonella enterica Paratyphi (S. Paratyphi), also called "typhoidal Salmonellae", causing systemic, life-threatening diseases in human, while others (non-typhoidal Salmonellae) infect a range of hosts and cause mild, self-limiting, gastroenteritis that could become severe in immunocompromised hostsFor decades, the research focussed on two major serovars: S. Typhi, for its paramount importance in human health, and on S. Typhimurium because is one of the most common in both human and animals. However, the information available thanks to the steep increase in genomic sequencing of clinical and environmental samples, have challenged a number of "dogmas" based on the Typhi/Typhimurium comparison. For example, the discovery that what was initially described as S. Typhi specific toxin, is also expressed by other 47 non-typhoidal serovars. This discovery pushed for a revision of the previous accepted model and spurred a plethora of new studies about the toxin role and its biology. In addition, the abundance of genomic data allowed us to study with good grade of confidence the relations between some virulence factors in the different serovars. Indeed, we have preliminary data showing that the acquisition of a virulence factor does not necessary result in increased virulence and some of them are functionally non compatible and we suggest that disease type (systemic or self-limiting) and severity are determined by the set of virulence factors "picked" during the evolution of a certain serovar.