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Title: The role of β-lactamases in carbapenem-resistant Gram-negative bacteria
Author: Walker, Rachel Anne
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1999
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In this thesis sixty-one clinical Pseudomonas aeruginosa isolates were acquired from hospitals within Japan and fifty-one of these strains were resistant to imipenem and/or meropenem (MIC >4mg/l). Neither IMP-1 nor a novel carbapenemase could be detected in any of these strains; instead synergism between a cephalosporinase and lowered outer membrane permeability was found to be the most prevalent mechanism of imipenem resistance. The carbapenem-hydrolysing metallo-β-lactamase produced by members of the genus Aeromonas have in the past few years demanded attention from a clinical and enzymological point of view. Two imipenem-resistant Aeromonas veronii biovar sobria strains 13 and 99 were isolated from a water source in South India. An imipenem-based detection method applied after isoelectric focusing revealed that a β-lactamase with a pI of 5.84 was responsible for carbapenem hydrolysis in strains 13 and 99 and unlike previously reported Aeromonas metallo-β-lactamases this enzyme could be detected with nitrocephin. Purification of this novel enzyme, nominated AVS-1, further demonstrated the unusual properties of this carbapenemase, most notably its insensitivity to EDTA. A metallo-β-lactamase gene was amplified from A. veronii bv. sobria strains 13 and 99 by PCR. Sequencing of the PCR product revealed that these two strains possess a metallo-β-lactamase gene that is closely related to the metallo-β-lactamase gene imiS previously identified in an isolate of A. veronii bv. sobria. Therefore, minor amino acid substitutions may account for the extended substrate specificity and unusual inhibitor profile of AVS-1. Two non-carbapenem-hydrolysing β-lactamases were also cloned from A. veronii bv. sobria strain 13. One of these β-lactamases a clavulanic acid sensitive β-lactamase was found to be an ampS-like penicillinase. The other cloned β-lactamase could unfortunately not be sequenced.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available