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，并将使用分子生物学、显微镜和生化技术来了解沙门氏菌血清型感染如何导致不同的表现。沙门氏菌属含有几种对人类和动物重要的病原体，是全球食源性疾病的最大贡献者之一。该属仅包括2个种：S.bongori和S.enterica。然而，肠炎沙门氏菌包含6个亚种和2000多个血清型，根据不同的表面抗原而具有不同的特征。重要的是，不同的血清型引起的疾病是非常不同的，一些如伤寒沙门氏菌和副伤寒沙门氏菌，也被称为“伤寒沙门氏菌”，引起系统性的，危及人类生命的疾病，而另一些(非伤寒沙门氏菌)感染一系列宿主，并引起轻微的，自限性的胃肠炎，可能会在免疫受损的宿主中变得严重。几十年来，研究集中在两个主要的血清型：伤寒沙门氏菌，因为它对人类健康非常重要，以及伤寒沙门氏菌，因为它在人类和动物中都是最常见的之一。然而，由于临床和环境样本的基因组测序急剧增加，现有的信息对基于伤寒/鼠伤寒比较的一些“教条”提出了挑战。例如，最初被描述为伤寒沙门氏菌特有毒素的发现，也在其他47个非伤寒血清型中表达。这一发现推动了对之前被接受的模型的修订，并引发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很好地研究不同血清型中一些毒力因子之间的关系。事实上，我们有初步数据表明，获得一种毒力因子并不一定会导致毒力增加，其中一些毒力因子在功能上是不相容的，我们认为，疾病类型(全身性或自限性)和严重程度是由在某个血清型进化过程中选择的一组毒力因子决定的。

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.