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Title: Novel antibacterial strategies with emphasis on the characterisation of β-lactamase inhibitors
Author: Payne, D. J.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2002
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This Thesis records my involvement and contributions to the discovery, evaluation and characterization of novel antibacterial strategies. My Ph.D. project focused on the characterization of a series of novel extended spectrum TEM/SHV β-lactamases and plasmid mediated Class C enzymes. This, coupled with research which I conducted in India on the prolific widespread carriage of resistant organisms, provided me with an excellent insight into the need for novel antibacterial agents to combat the rising tide of resistant organisms. Subsequently, on joining SmithKline Beecham in 1990 I performed research that led to the discovery and characterization of a variety of novel inhibitors of serine β-lactamases. I also led a research initiative which successfully characterized a variety of new metallo-β-lactamases and identified novel inhibitors of this group of β-lactamases. Furthermore, these compounds demonstrated some potential for combating this emerging resistance mechanism. In 1995 my interests focused on the exploitation of bacterial genomics for the identification and characterization of novel antibacterial targets. I initiated projects to evaluate fatty acid biosynthesis, cell wall biosynthesis, aromatic amino acid biosynthesis, cell division and protein secretion as antibacterial strategies. This work provided the first ever identification and characterization of the Gram positive cocci homologs of FabI (enoyl ACP reductase, fatty acid biosynthesis), MurA (UDP-N-acetylglucosamine enolpyruvyl transferase, peptidoglycan biosynthesis), EPSP synthase (5-enolpyruvylshikimate-3-phosphate synthase, aromatic amino acid biosynthesis), FtsA, FtsZ (cell division) and SRP (signal recognition particle, protein secretion). It is my hope that this work will either directly or indirectly facilitate the discovery of pioneer antibacterial agents urgently required for our battle against bacterial pathogens in the next millennium.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (D.Sc.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available