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Title: Fluoroquinolone action and resistance : action of ciprofloxacin in a standard Escherichia coli and the roles of GyrA and ParC mutations in high-level resistance
Author: Pirapatrungsuriya, Komson
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1998
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Bacterial isolates from Malaysia and Thailand were obtained, characterised and tested for their MIC of ciprofloxacin (Cip). Some were found to be extremely resistant including three Acinetobacter baumannii (MIC of 128 mg/L). GyrA and parC are homologous genes and are subunits of enzyme DNA gyrase and topoisomerase IV, respectively. Three E. coli (MIC of 128 mg/L) had two mutations in GyrA (Ser-83 to Leu and Asp-87 to Tyr) and one mutation in parC (Ser-83 to lle). Another E. coli (MIC of 32 mg/L) had the same three mutations except at gyrA 87 mutation was Asp-87 to Asn. This Tyr substitution seems to enhance resistance more than any other mutations. One Citrobacter freundii (MIC of 128 mg/L) had Thr-83 to Ile and Asp-87 to Tyr; and no mutation in parC's QRDR. Enterobacter sakazakii (MIC of 32 mg/L) had two mutations in GyrA's QRDR. Ser-83 to Tyr and Asp-87 to Asn, and one mutation in parC's QRDR: Ser-83 to Ile. Moreover, one Moraxella catarrhalis (found in Edinburgh) with high Cip resistant with an MIC of 4.0 mg/L had one mutation in gyrA's QRDR: Gly-87 to Asn, but its parC's QRDR could not be identified. Mutations in both gyrA's and parC's QRDR at amino acid residues 83 and 87 are probably the main mechanism of Cip resistance of those isolates tested. (Amino acid positions appeared above are those equivalent to E. coli's gyrA). GyrA's and parC's QRDR of C. freundii and Ent. sakazakii, and also gyrA's QRDR of Moraxella catarrhalis were revealed perhaps first time. Unique gyrA silent-nucleotide alterations of eight E. coli from Malaysia and Thailand were found to be common to both sensitive and resistant isolates at position 438, 456, 483 and 516, which differed from all E. coli published sequences in GenBANK. These results throw light on molecular integrity of E. coli. Fluoroquinolone action was also examined in the standard E. coli strain NCTC10418. Mutual antagonism between chloramphenicol (Cm) and rifampicin (Rif) against Cip was examined on E. coli NCTC10418.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available