Characterisation and Mechanism of Action Investigation of Novel Rhenium-containing Antibiotics

Antimicrobial resistance(AMR) poses a significant global threat to public health, necessitating innovative strategies to combat the rise of multidrug-resistant pathogens. This thesis investigates the use of two novel Rhenium-complexed antibiotic derivatives as potential antimicrobials to address the challenges associated with antibiotic resistance. The research involves a comprehensive comparison study, examining the behaviour of bacteria under varying concentrations of these rhenium complexes. The study employs a range of analytical techniques, including Minimal Inhibitory Concentration (MIC) assays, Growth curve analysis, Bacterial Cytological Profiling (BCP) and Protein Localization studies by performing single cell fluorescence imaging, DiSC3(5) diffusion assay, Propidium Iodide Assay, Single Molecule Localization Imaging, and DNA Compaction Analysis. These diverse methodologies offer a holistic understanding of the antimicrobial efficacy and mechanisms of action of the novel rhenium-based compounds. While rhenium has been studied for its promising anticancer effects, a comprehensive exploration of its full therapeutic potential is lacking. This thesis emphasizes the need for further research to uncover the untapped capabilities of rhenium, particularly in the context of combating antibiotic resistance. The findings of this study contribute valuable insights into the development of alternative antimicrobial agents and underscore the importance of exploring unconventional metal-based complexes as potential solutions to the escalating antibiotic resistance crisis. While one of the rhenium derivatives is fully characterized, the complete structure of the other is withheld due to its significant potential in future applications. Furthermore, during this study a new quantification tool for image analysis of fluorescence microscopy data was utilized based on an ImageJ macro originally developed by J. Grimshaw, Newcastle University. This new method enables the quantification of nucleoid compaction from fluorescence microscopy images of bacterial cells, aiding the identification of antibiotic effects that could not be observed by eye.