Genetic factors that determine host resistance to bacterial infection

Student thesis: Master's Thesis

Abstract

Antibiotic resistance is one of the major challenges that we face today. Not only in a medical sense, but also for a country’s national security, as the use of a bioweapon is an ever increasing concern. To help combat these threats, understanding how bacteria interact with their host could be a key research area. By understanding which human genes confer resistance or susceptibility to bacteria during infection could possibly lead the way in developing new drug targets to stop infection. This thesis focuses on Salmonella enterica serovar typhimurium infection of U937 cells and examines the role the gene SLC7A11 plays in the infection process a previous work identified that SLC7A11 gene mutations decreased susceptibility to infection. SLC7A11 CRISPR #1 U937 cells were infected with Salmonella enterica serovar typhimurium to help understand if this gene did provide resistance when knocked out. This infection was carried out alongside WT U937 cells and WT U937 cells which were both exposed to Salmonella enterica serovar typhimurium with the drug sulfasalazine. This drug is a known inhibitor of SLC7A11. From the results it can be seen that inhibition of SLC7A11 may cause a trend towards beneficial effects in stopping the infection of macrophages by Salmonella enterica serovar typhimurium. However, with p-values of 0.60 for 5 ng/ml of sulfasalazine, 0.11 for 10 ng/ml of sulfasalazine and 0.06 for SLC7A11 knockout, our current findings are not statistically significant. In conclusion, the inhibition of SLC7A11 by sulfasalazine may inhibit the infection of macrophages by the infecting bacteria Salmonella enterica serovar typhimurium. This could lead to the development of host directed therapies to combat bacterial infection, with the use of pharmaceutical inhibitors of not only SLC7A11 but also other identified genes.
Date of Award9 Jun 2022
Original languageEnglish
Awarding Institution
  • University Of Strathclyde

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