{"id":{"repo_id":"sask","oai_identifier":"oai:harvest.usask.ca:10388/ETD-2012-04-434"},"canonical_url":"https://search.dev.ndltd.org/etd/sask/oai:harvest.usask.ca:10388/ETD-2012-04-434","repository":{"repo_id":"sask","name":"University of Saskatchewan","base_url":"https://harvest.usask.ca/server/oai/request"},"display":{"title":"Generation of SOS inhibitors as co-drugs to potentiate the activity of bactericidal antibiotics and to block the emergence of antibiotic resistance","abstract":"The rapidly increasing emergence of antibiotic resistance amongst pathogenic bacteria is a major clinical and public health problem. The increase in resistant pathogens, accompanied with the small number of new antibiotics introduced in recent years, has limited the number of effective antimicrobials. The classical paradigm suggests that antibiotic resistance emerges by selection for pre-existing mutants in the bacterial population exposed to antibiotics. In contrast, recent data suggested that mutations evolve after cells encounter antibiotic therapy. This kind of mutation is known as adaptive mutation, which is activated by the SOS DNA repair and mutagenesis pathways. Accumulation of single-stranded DNA (ss-DNA) is the signal that induces the SOS response by promoting the formation of the RecA filament, which in turn activates the auto-cleavage activity of LexA and allows expression of SOS genes, including the SOS error-prone polymerases. In this project, phthalocyanine tetrasulfonic acid (PcTs)-based RecA inhibitors were characterized. PcTs molecules were found to potentiate the activity of bactericidal antibiotics and reduce the ability of bacteria to acquire antibiotic resistance mutations. This study highlights the ability of RecA inhibitors to potentiate the activity of antibiotics and provides a strategy for prolonging the life span of existing and newly developed antibiotics. We predicate that RecA inhibitors will be part of an antibiotic “cocktail” that enhances the activity of antibiotics and blocks resistance, which will ultimately prolong antibiotic lifespan.","abstract_html":"The rapidly increasing emergence of antibiotic resistance amongst pathogenic bacteria is a major clinical and public health problem. The increase in resistant pathogens, accompanied with the small number of new antibiotics introduced in recent years, has limited the number of effective antimicrobials. The classical paradigm suggests that antibiotic resistance emerges by selection for pre-existing mutants in the bacterial population exposed to antibiotics. In contrast, recent data suggested that mutations evolve after cells encounter antibiotic therapy. This kind of mutation is known as adaptive mutation, which is activated by the SOS DNA repair and mutagenesis pathways. Accumulation of single-stranded DNA (ss-DNA) is the signal that induces the SOS response by promoting the formation of the RecA filament, which in turn activates the auto-cleavage activity of LexA and allows expression of SOS genes, including the SOS error-prone polymerases. In this project, phthalocyanine tetrasulfonic acid (PcTs)-based RecA inhibitors were characterized. PcTs molecules were found to potentiate the activity of bactericidal antibiotics and reduce the ability of bacteria to acquire antibiotic resistance mutations. This study highlights the ability of RecA inhibitors to potentiate the activity of antibiotics and provides a strategy for prolonging the life span of existing and newly developed antibiotics. We predicate that RecA inhibitors will be part of an antibiotic “cocktail” that enhances the activity of antibiotics and blocks resistance, which will ultimately prolong antibiotic lifespan.","abstract_has_math":false,"creators":["Alhhazmi, Areej"],"institution":"University of Saskatchewan","degree_name":"Master of Science (M.Sc.)","degree_level":"Masters","degree_discipline":"Health Sciences","degree_department":null,"school":null,"contributors":[],"advisors":["Geyer, Ron"],"committee_chairs":[],"committee_members":["Blondeau, Joseph","Bull, Harold","Sanche, Stephen","DeCoteau, John"],"year":2013,"date_issued":"2013-07-29","date_published":"2013-07-29","updated_at":"2026-07-24T04:27:01Z","subjects":["adaptive mutations, the SOS system, resistance, potentiation, antibiotics"],"languages":["eng"],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://hdl.handle.net/10388/ETD-2012-04-434","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Geyer, Ron"]},{"key":"dc:contributor.committeemember","label":"Committee Member","values":["Blondeau, Joseph","Bull, Harold","Sanche, Stephen","DeCoteau, John"]},{"key":"dc:creator","label":"Author","values":["Alhhazmi, Areej"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2013-09-16T19:52:05Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2013-09-16T19:52:05Z"]},{"key":"dc:date.issued","label":"Date","values":["2013-07-29"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Health Sciences"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Masters"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Master of Science (M.Sc.)"]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["University of Saskatchewan"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["adaptive mutations, the SOS system, resistance, potentiation, antibiotics"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language.iso","label":"Language (ISO)","values":["eng"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://hdl.handle.net/10388/ETD-2012-04-434"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["The rapidly increasing emergence of antibiotic resistance amongst pathogenic bacteria is a major clinical and public health problem. The increase in resistant pathogens, accompanied with the small number of new antibiotics introduced in recent years, has limited the number of effective antimicrobials. The classical paradigm suggests that antibiotic resistance emerges by selection for pre-existing mutants in the bacterial population exposed to antibiotics. In contrast, recent data suggested that mutations evolve after cells encounter antibiotic therapy. This kind of mutation is known as adaptive mutation, which is activated by the SOS DNA repair and mutagenesis pathways. Accumulation of single-stranded DNA (ss-DNA) is the signal that induces the SOS response by promoting the formation of the RecA filament, which in turn activates the auto-cleavage activity of LexA and allows expression of SOS genes, including the SOS error-prone polymerases. In this project, phthalocyanine tetrasulfonic acid (PcTs)-based RecA inhibitors were characterized. PcTs molecules were found to potentiate the activity of bactericidal antibiotics and reduce the ability of bacteria to acquire antibiotic resistance mutations. This study highlights the ability of RecA inhibitors to potentiate the activity of antibiotics and provides a strategy for prolonging the life span of existing and newly developed antibiotics. We predicate that RecA inhibitors will be part of an antibiotic “cocktail” that enhances the activity of antibiotics and blocks resistance, which will ultimately prolong antibiotic lifespan."]},{"key":"dc:title","label":"Title","values":["Generation of SOS inhibitors as co-drugs to potentiate the activity of bactericidal antibiotics and to block the emergence of antibiotic resistance"]}]}],"canonical_facts":{"dc:contributor.advisor":["Geyer, Ron"],"dc:contributor.committeemember":["Blondeau, Joseph","Bull, Harold","Sanche, Stephen","DeCoteau, John"],"dc:creator":["Alhhazmi, Areej"],"dc:date.accessioned":["2013-09-16T19:52:05Z"],"dc:date.available":["2013-09-16T19:52:05Z"],"dc:date.issued":["2013-07-29"],"dc:description.abstract":["The rapidly increasing emergence of antibiotic resistance amongst pathogenic bacteria is a major clinical and public health problem. The increase in resistant pathogens, accompanied with the small number of new antibiotics introduced in recent years, has limited the number of effective antimicrobials. The classical paradigm suggests that antibiotic resistance emerges by selection for pre-existing mutants in the bacterial population exposed to antibiotics. In contrast, recent data suggested that mutations evolve after cells encounter antibiotic therapy. This kind of mutation is known as adaptive mutation, which is activated by the SOS DNA repair and mutagenesis pathways. Accumulation of single-stranded DNA (ss-DNA) is the signal that induces the SOS response by promoting the formation of the RecA filament, which in turn activates the auto-cleavage activity of LexA and allows expression of SOS genes, including the SOS error-prone polymerases. In this project, phthalocyanine tetrasulfonic acid (PcTs)-based RecA inhibitors were characterized. PcTs molecules were found to potentiate the activity of bactericidal antibiotics and reduce the ability of bacteria to acquire antibiotic resistance mutations. This study highlights the ability of RecA inhibitors to potentiate the activity of antibiotics and provides a strategy for prolonging the life span of existing and newly developed antibiotics. We predicate that RecA inhibitors will be part of an antibiotic “cocktail” that enhances the activity of antibiotics and blocks resistance, which will ultimately prolong antibiotic lifespan."],"dc:identifier.uri":["https://hdl.handle.net/10388/ETD-2012-04-434"],"dc:language.iso":["eng"],"dc:subject":["adaptive mutations, the SOS system, resistance, potentiation, antibiotics"],"dc:title":["Generation of SOS inhibitors as co-drugs to potentiate the activity of bactericidal antibiotics and to block the emergence of antibiotic resistance"],"thesis:degree_discipline":["Health Sciences"],"thesis:degree_level":["Masters"],"thesis:degree_name":["Master of Science (M.Sc.)"],"thesis:institution_name":["University of Saskatchewan"]},"updated_at":"2026-07-24T04:27:01Z"}