Antimicrobials and antimicrobial resistance: two studies investigating different ways to tackle the issue

The discovery of antimicrobials revolutionised the world of medicine on a global scale. However, with the growing prevalence of antimicrobial resistance we are seeing an increase in bacteria that are multidrug resistant and can worryingly be resistant to our ‘last-resort’ drugs. This thesis looks at two different ways to tackle the antimicrobial resistance crisis. The first investigated using polymer nanoparticle drug delivery systems as a way to improve antimicrobial delivery to Helicobacter pylori. The aim of the project was to improve the gastric retention and reduce the exposure of commensal bacteria to antimicrobial drugs. This should reduce side effects and allow a lower concentration of drug to be administered. A novel polymer drug delivery system was synthesised and loaded with Linoleic acid (LLA), an antimicrobial fatty acid, and assessed its ability to kill H. pylori in vitro. The results showed both LLA loaded and unloaded nanoparticles had the ability to eradicate H. pylori. The second project worked on prevention of disease by the development of vaccines. Outer membrane vesicles (OMVs) have shown promise as vaccines against a number of bacterial species. This project focused on detoxifying the LPS of Salmonella enteritica serovar Typhimurium and creating OMVs. To do this the genes msbB, pagP and tolR were attempted to be knocked out. Unfortunately, we were unable to knock out msbB. These two projects highlight two key ways of tackling antimicrobial resistance, developing new therapeutics and preventing disease. A global effort must be made to combat this issue or we could see a return to the pre-antibiotic era