The development of new drug leads to combat bacterial resistance towards antibiotics

Vella, Peter (2012). The development of new drug leads to combat bacterial resistance towards antibiotics PhD Thesis, School of Chemistry & Molecular Bioscience, The University of Queensland.

       
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Author Vella, Peter
Thesis Title The development of new drug leads to combat bacterial resistance towards antibiotics
School, Centre or Institute School of Chemistry & Molecular Bioscience
Institution The University of Queensland
Publication date 2012
Thesis type PhD Thesis
Supervisor Gary Schenk
Ross McGeary
Total pages 255
Total colour pages 72
Total black and white pages 183
Language eng
Subjects 060112 Structural Biology (incl. Macromolecular Modelling)
030405 Molecular Medicine
060107 Enzymes
Formatted abstract
Penicillin and other beta-lactam antibiotics have become the 'gold standard' for the treatment of bacterial infections. This thesis examines the metallo-beta-lactamases (MBLs), which allow bacteria to resist the action of beta-lactam antibiotics. The MBLs are introduced along with a review of research in this field in chapter one. Chapter two describes the identification, kinetic characterisation and modelling of small molecule fragments for the development of inhibitors against MBLs. Chapter three focuses on the identification, modelling and characterisation of new lactamases from both clinical and environmental sources. Chapter four describes stopped-flow kinetic studies into IMP-1 using clinically relevant substrates in order to gain an understanding of the mechanism of IMP-1.

The aims of this research may broadly be summarised as follows: (a) identify fragment compounds of interest so that the groundwork may be laid for the development of more potent inhibitors for clinically relevant MBLs; (b) probe the mechanisms of MBLs using stopped flow studies using clinically relevant substrates and (c) explore the under-characterised and novel MBLs from clinical settings and the wider environment.
Keyword Antibiotic resistance
Fragment-based screening
Docking
Metallo-beta-lactamases
Metallo-enzymes

 
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Created: Wed, 24 Oct 2012, 11:20:33 EST by Mr Peter Vella on behalf of Scholarly Communication and Digitisation Service