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Selected β-lactam resistance in selected species of gram-negative bacteria
The molecular basis of β-lactam resistance was investigated in this study. Selected gram-negative clinical isolates potentially displaying therapeutic problems were chosen as the subjects. Clinical diagnostic tests are not always very accurate and informative about the molecular nature of β-lactam r...
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| Format: | Thesis |
| Language: | English English |
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Department of Clinical Laboratory Sciences
2026
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| _version_ | 1867613343267684352 |
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| access_status_str | Open Access |
| author | Nelson, Elton |
| author2 | Elisha, B.G |
| author_browse | Elisha, B.G Nelson, Elton |
| author_facet | Elisha, B.G Nelson, Elton |
| author_sort | Nelson, Elton |
| collection | Thesis |
| description | The molecular basis of β-lactam resistance was investigated in this study. Selected gram-negative clinical isolates potentially displaying therapeutic problems were chosen as the subjects. Clinical diagnostic tests are not always very accurate and informative about the molecular nature of β-lactam resistance, thus molecular investigations are carried out to more fully and comprehensibly explain the clinically observed phenomena. In the view of Enterobacteria being some of the most commonly isolated, clinically problematic, bacteria, E. coli and K. pneumoniae isolates with unusual β-lactam resistance profiles were investigated. The first cluster of E. coli isolates were investigated with respect to their resistance to the cephalosporins and the cephamycin, cefoxitin. β-lactamase promoter mutations were identified and expression studies were performed to corroborate overexpression of the AmpC enzyme. The second group of E. coli isolates displayed resistance to the inhibitor combination, amoxicillin-clavulanate. In this group, the resistance genes were identified, with their promoters. Resistance was attributed to TEM overproduction and overproduction of a specially adapted TEM (IRTs) β-lactamase. Primer extension was used to determine the transcriptional start site of the IRT. The K. pneumoniae isolates were investigated for their resistance to the cephalosporins, cefoxitin and amoxicillin clavulanate. The resistance was attributed to an interplay of β-lactamase production and the loss of permeability. Since A. baumannii is becoming an increasingly popular opportunistic pathogen in the clinical setting, strain RAN was also investigated. The presence of β-lactamase resistance genes was investigated. The chromosomal ampC gene was confirmed to be present, cloned and sequenced. The regulation of the ampC gene was examined. The ampC gene was also studied in terms of its genetic context. Sequence analysis suggests that the ampC might be associated with a stabilized transposition event. |
| format | Thesis |
| id | oai:open.uct.ac.za:11427/43214 |
| institution | University of Cape Town (South Africa) |
| language | English eng |
| last_indexed | 2026-06-10T12:34:38.153Z |
| license_str | Not specified — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from UCTD — University of Cape Town Open Access Repository |
| publishDate | 2026 |
| publishDateRange | 2026 |
| publishDateSort | 2026 |
| publisher | Department of Clinical Laboratory Sciences |
| publisherStr | Department of Clinical Laboratory Sciences |
| record_format | dspace |
| source_str | UCTD — University of Cape Town Open Access Repository |
| spelling | oai:open.uct.ac.za:11427/43214 Selected β-lactam resistance in selected species of gram-negative bacteria Nelson, Elton Elisha, B.G Bacteria antibiotics enzymes The molecular basis of β-lactam resistance was investigated in this study. Selected gram-negative clinical isolates potentially displaying therapeutic problems were chosen as the subjects. Clinical diagnostic tests are not always very accurate and informative about the molecular nature of β-lactam resistance, thus molecular investigations are carried out to more fully and comprehensibly explain the clinically observed phenomena. In the view of Enterobacteria being some of the most commonly isolated, clinically problematic, bacteria, E. coli and K. pneumoniae isolates with unusual β-lactam resistance profiles were investigated. The first cluster of E. coli isolates were investigated with respect to their resistance to the cephalosporins and the cephamycin, cefoxitin. β-lactamase promoter mutations were identified and expression studies were performed to corroborate overexpression of the AmpC enzyme. The second group of E. coli isolates displayed resistance to the inhibitor combination, amoxicillin-clavulanate. In this group, the resistance genes were identified, with their promoters. Resistance was attributed to TEM overproduction and overproduction of a specially adapted TEM (IRTs) β-lactamase. Primer extension was used to determine the transcriptional start site of the IRT. The K. pneumoniae isolates were investigated for their resistance to the cephalosporins, cefoxitin and amoxicillin clavulanate. The resistance was attributed to an interplay of β-lactamase production and the loss of permeability. Since A. baumannii is becoming an increasingly popular opportunistic pathogen in the clinical setting, strain RAN was also investigated. The presence of β-lactamase resistance genes was investigated. The chromosomal ampC gene was confirmed to be present, cloned and sequenced. The regulation of the ampC gene was examined. The ampC gene was also studied in terms of its genetic context. Sequence analysis suggests that the ampC might be associated with a stabilized transposition event. 2026-05-08T13:38:44Z 2026-05-08T13:38:44Z 2004 2026-05-08T13:32:37Z Thesis / Dissertation Doctoral PhD http://hdl.handle.net/11427/43214 en eng application/pdf Department of Clinical Laboratory Sciences Faculty of Health Sciences University of Cape Town |
| spellingShingle | Bacteria antibiotics enzymes Nelson, Elton Selected β-lactam resistance in selected species of gram-negative bacteria |
| thesis_degree_str | Doctoral |
| title | Selected β-lactam resistance in selected species of gram-negative bacteria |
| title_full | Selected β-lactam resistance in selected species of gram-negative bacteria |
| title_fullStr | Selected β-lactam resistance in selected species of gram-negative bacteria |
| title_full_unstemmed | Selected β-lactam resistance in selected species of gram-negative bacteria |
| title_short | Selected β-lactam resistance in selected species of gram-negative bacteria |
| title_sort | selected β lactam resistance in selected species of gram negative bacteria |
| topic | Bacteria antibiotics enzymes |
| url | http://hdl.handle.net/11427/43214 |
| work_keys_str_mv | AT nelsonelton selectedblactamresistanceinselectedspeciesofgramnegativebacteria |