{"id":{"repo_id":"the-open-u","oai_identifier":"oai:oro.open.ac.uk:54640"},"canonical_url":"https://search.dev.ndltd.org/etd/the-open-u/oai:oro.open.ac.uk:54640","repository":{"repo_id":"the-open-u","name":"The Open University","base_url":"https://oro.open.ac.uk/cgi/oai2"},"display":{"title":"The emergence of Escherichia coli with CTX-M extended-spectrum beta-lactamases in the United Kingdom","abstract":"In the past decade, multi-resistant Escherichia coli with CTX-M enzymes have rapidly become the leading producers of extended-spectrum β-Iactamases (ESBLs) worldwide. E. coli with CTX-M-15 β-Iactamases are the most common, and are now endemic in many UK hospitals and in the community. Their epidemiology is complex, including five major epidemic clones as defined by pulsed-field gel electrophoresis, as well as many unrelated producers. This study sought to characterise, at a molecular level, E. coli isolates with CTX-M ESBLs and to investigate their nationwide dissemination, so as to identify the basis for the clinical success of thest? organisms. The molecular mechanisms responsible for the multi-drug resistance phrnotype of representative isolates with CTX-M enzymes were explored and compared, as were their phylogenetic and virulence backgrounds. The genetic support and environment of the various blaCTX-M genes were also investigated.
The multi-drug resistance of E. coli with CTX-M enzymes was principally encoded by single plasmids, generally self-transferable. Among producers of CTX-M-15 enzyme, and regardless of their host strain's epidemic status, these plasmids were closely-related (IncFII) and encoded most often blaTEM-1, blaOXA-1 along blaCTX-M-15, as well as aac(6')-Ib-cr, aac(3)-IIa and tet(A). The most prevalent UK clone (A) expressed a lower level of CTX-M-15 enzyme than most other producers, probably owing to an IS26 element located downstream of the gene's normal promoter. Its CTX-M-15-encoding plasmid was not self-transferable in-vitro, but carried twelve genes effecting resistance to eight classes of antibiotics, as well as genes for virulence determinents. Most E. coli with CTX-M enzymes, including the major epidemic clones, belonged to the virulence-associated phylogenetic group B2 or D, but did not harbour more virulence determinants than B2 isolates with non-CTX-M ESBLs. Although related, three slightly distinct virulence profiles were apparent for clonal and non-clonal isolates with CTX-M-15 enzymes.
In conclusion, CTX-M ESBLs have rapidly spread in the UK among virulent E. coli isolates, aided by horizontal transfer of multi-resistance plasmids, as well as by clonal spread of epidemic producer strains. Their dissemination worryingly undermines the success of antibiotic therapy, especially in community patients, where few oral options remain.","abstract_html":"In the past decade, multi-resistant <i>Escherichia coli</i> with CTX-M enzymes have rapidly become the leading producers of extended-spectrum β-Iactamases (ESBLs) worldwide. <i>E. coli</i> with CTX-M-15 β-Iactamases are the most common, and are now endemic in many UK hospitals and in the community. Their epidemiology is complex, including five major epidemic clones as defined by pulsed-field gel electrophoresis, as well as many unrelated producers. This study sought to characterise, at a molecular level, <i>E. coli</i> isolates with CTX-M ESBLs and to investigate their nationwide dissemination, so as to identify the basis for the clinical success of thest? organisms. The molecular mechanisms responsible for the multi-drug resistance phrnotype of representative isolates with CTX-M enzymes were explored and compared, as were their phylogenetic and virulence backgrounds. The genetic support and environment of the various <sup><i>bla</i></sup><sub>CTX-M</sub> genes were also investigated.<br></br><br></br> The multi-drug resistance of <i>E. coli</i> with CTX-M enzymes was principally encoded by single plasmids, generally self-transferable. Among producers of CTX-M-15 enzyme, and regardless of their host strain's epidemic status, these plasmids were closely-related (IncFII) and encoded most often <i>bla</i><sub>TEM-1</sub>, <i>bla</i><sub>OXA-1</sub> along <i>bla</i><sub>CTX-M-15</sub>, as well as <i>aac(6')-Ib-cr, aac(3)-IIa</i> and <i>tet</i>(A). The most prevalent UK clone (A) expressed a lower level of CTX-M-15 enzyme than most other producers, probably owing to an IS<i>26</i> element located downstream of the gene's normal promoter. Its CTX-M-15-encoding plasmid was not self-transferable <i>in-vitro</i>, but carried twelve genes effecting resistance to eight classes of antibiotics, as well as genes for virulence determinents. Most <i>E. coli</i> with CTX-M enzymes, including the major epidemic clones, belonged to the virulence-associated phylogenetic group B2 or D, but did not harbour more virulence determinants than B2 isolates with non-CTX-M ESBLs. Although related, three slightly distinct virulence profiles were apparent for clonal and non-clonal isolates with CTX-M-15 enzymes. <br></br><br></br>In conclusion, CTX-M ESBLs have rapidly spread in the UK among virulent <i>E. coli</i> isolates, aided by horizontal transfer of multi-resistance plasmids, as well as by clonal spread of epidemic producer strains. Their dissemination worryingly undermines the success of antibiotic therapy, especially in community patients, where few oral options remain.","abstract_has_math":false,"creators":["Karisik, Edi"],"institution":"The Open University","degree_name":"phd","degree_level":"doctoral","degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2007,"date_issued":"2007","date_published":"2007","updated_at":"2026-07-24T05:02:45Z","subjects":[],"languages":["en"],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":null,"outbound_label":null,"outbound_source":null},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:creator","label":"Author","values":["Karisik, Edi"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2007"]},{"key":"dc:date.issued","label":"Date","values":["2007"]},{"key":"dc:publisher.institution","label":"Dc Publisher Institution","values":["The Open University"]},{"key":"dc:relation.isreferencedby","label":"Dc Relation Isreferencedby","values":["https://oro.open.ac.uk/54640/"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]},{"key":"dc:type.qualificationlevel","label":"Dc Type Qualificationlevel","values":["doctoral"]},{"key":"dc:type.qualificationname","label":"Dc Type Qualificationname","values":["phd"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["en"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://oro.open.ac.uk/54640/1/486507.pdf"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["In the past decade, multi-resistant Escherichia coli with CTX-M enzymes have rapidly become the leading producers of extended-spectrum β-Iactamases (ESBLs) worldwide. E. coli with CTX-M-15 β-Iactamases are the most common, and are now endemic in many UK hospitals and in the community. Their epidemiology is complex, including five major epidemic clones as defined by pulsed-field gel electrophoresis, as well as many unrelated producers. This study sought to characterise, at a molecular level, E. coli isolates with CTX-M ESBLs and to investigate their nationwide dissemination, so as to identify the basis for the clinical success of thest? organisms. The molecular mechanisms responsible for the multi-drug resistance phrnotype of representative isolates with CTX-M enzymes were explored and compared, as were their phylogenetic and virulence backgrounds. The genetic support and environment of the various blaCTX-M genes were also investigated.
The multi-drug resistance of E. coli with CTX-M enzymes was principally encoded by single plasmids, generally self-transferable. Among producers of CTX-M-15 enzyme, and regardless of their host strain's epidemic status, these plasmids were closely-related (IncFII) and encoded most often blaTEM-1, blaOXA-1 along blaCTX-M-15, as well as aac(6')-Ib-cr, aac(3)-IIa and tet(A). The most prevalent UK clone (A) expressed a lower level of CTX-M-15 enzyme than most other producers, probably owing to an IS26 element located downstream of the gene's normal promoter. Its CTX-M-15-encoding plasmid was not self-transferable in-vitro, but carried twelve genes effecting resistance to eight classes of antibiotics, as well as genes for virulence determinents. Most E. coli with CTX-M enzymes, including the major epidemic clones, belonged to the virulence-associated phylogenetic group B2 or D, but did not harbour more virulence determinants than B2 isolates with non-CTX-M ESBLs. Although related, three slightly distinct virulence profiles were apparent for clonal and non-clonal isolates with CTX-M-15 enzymes.
In conclusion, CTX-M ESBLs have rapidly spread in the UK among virulent E. coli isolates, aided by horizontal transfer of multi-resistance plasmids, as well as by clonal spread of epidemic producer strains. Their dissemination worryingly undermines the success of antibiotic therapy, especially in community patients, where few oral options remain."]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["The emergence of Escherichia coli with CTX-M extended-spectrum beta-lactamases in the United Kingdom"]}]}],"canonical_facts":{"dc:creator":["Karisik, Edi"],"dc:date":["2007"],"dc:date.issued":["2007"],"dc:description.abstract":["In the past decade, multi-resistant Escherichia coli with CTX-M enzymes have rapidly become the leading producers of extended-spectrum β-Iactamases (ESBLs) worldwide. E. coli with CTX-M-15 β-Iactamases are the most common, and are now endemic in many UK hospitals and in the community. Their epidemiology is complex, including five major epidemic clones as defined by pulsed-field gel electrophoresis, as well as many unrelated producers. This study sought to characterise, at a molecular level, E. coli isolates with CTX-M ESBLs and to investigate their nationwide dissemination, so as to identify the basis for the clinical success of thest? organisms. The molecular mechanisms responsible for the multi-drug resistance phrnotype of representative isolates with CTX-M enzymes were explored and compared, as were their phylogenetic and virulence backgrounds. The genetic support and environment of the various blaCTX-M genes were also investigated.
The multi-drug resistance of E. coli with CTX-M enzymes was principally encoded by single plasmids, generally self-transferable. Among producers of CTX-M-15 enzyme, and regardless of their host strain's epidemic status, these plasmids were closely-related (IncFII) and encoded most often blaTEM-1, blaOXA-1 along blaCTX-M-15, as well as aac(6')-Ib-cr, aac(3)-IIa and tet(A). The most prevalent UK clone (A) expressed a lower level of CTX-M-15 enzyme than most other producers, probably owing to an IS26 element located downstream of the gene's normal promoter. Its CTX-M-15-encoding plasmid was not self-transferable in-vitro, but carried twelve genes effecting resistance to eight classes of antibiotics, as well as genes for virulence determinents. Most E. coli with CTX-M enzymes, including the major epidemic clones, belonged to the virulence-associated phylogenetic group B2 or D, but did not harbour more virulence determinants than B2 isolates with non-CTX-M ESBLs. Although related, three slightly distinct virulence profiles were apparent for clonal and non-clonal isolates with CTX-M-15 enzymes.
In conclusion, CTX-M ESBLs have rapidly spread in the UK among virulent E. coli isolates, aided by horizontal transfer of multi-resistance plasmids, as well as by clonal spread of epidemic producer strains. Their dissemination worryingly undermines the success of antibiotic therapy, especially in community patients, where few oral options remain."],"dc:format":["application/pdf"],"dc:identifier.uri":["https://oro.open.ac.uk/54640/1/486507.pdf"],"dc:language":["en"],"dc:publisher.institution":["The Open University"],"dc:relation.isreferencedby":["https://oro.open.ac.uk/54640/"],"dc:title":["The emergence of Escherichia coli with CTX-M extended-spectrum beta-lactamases in the United Kingdom"],"dc:type":["Thesis"],"dc:type.qualificationlevel":["doctoral"],"dc:type.qualificationname":["phd"]},"updated_at":"2026-07-24T05:02:45Z"}