An Analysis of Salmonella from Molecular, Cellular, and Food Safety Perspectives

Abstract

Salmonella is a major foodborne pathogen in both developing and developed countries and is responsible for a range of diseases including enteric fever, gastroenteritis, and bacteremia. Despite advancements in food safety strategies, Salmonella illness continues to substantially contribute to foodborne related hospitalization and deaths in both Canada and the United States. While a majority of these illnesses are associated with the mishandling of raw meat, a large portion are related to outbreaks from incidental contamination of food products. In Canada, these contaminated products are recalled from retailers by the Canadian Food Inspection Agency to prevent the transmission of Salmonella. However, not all Salmonella contribute to severe health outcomes as there is a large degree of genetic heterogeneity among the 2600 serovars within the genus. This range in genetic variability across Salmonella serovars is linked to numerous genetic elements that dictate virulence. How these elements collectively constitute Salmonella disease is not completely understood. Several genetic elements encode highly studied virulence factors, such as Salmonella pathogenicity island 1 and 2, with well documented contributions to pathogenesis. However, many genetic elements implicated in Salmonella virulence remain uncharacterized. Identifying how these potential virulence factors contribute to Salmonella disease is essential to understanding the virulence disparity between serovars. In this thesis I analyze Salmonella from molecular, cellular, and food safety perspectives to investigate some of these research questions. First, I examine the contributions of Salmonella to microbial-related recalls in Canada from 2000-2017 in which I highlight recent increases in Salmonella-related recalls involving fruits, vegetables, and leafy greens. Second, I discuss my research on evaluating protozoa as a screening model for Salmonella virulence and present the Acanthamoeba screening model I developed to characterize the virulence of clinical and environment isolates of Salmonella. Third, I explore the role of the E3 ubiquitin ligase effector SspH1 during Salmonella infection and demonstrate that it stimulates degradation of the host kinase PKN1. In addition, I investigate the prevalence of sspH1 in a large collection of Salmonella isolates (the Syst-OMICS consortium) and reveal a potentially new SspH1-related protein. Lastly, I propose future directions related to the work presented in my thesis.