{"id":{"repo_id":"vt","oai_identifier":"oai:vtechworks.lib.vt.edu:10919/121112"},"canonical_url":"https://search.dev.ndltd.org/etd/vt/oai:vtechworks.lib.vt.edu:10919/121112","repository":{"repo_id":"vt","name":"Virginia Tech","base_url":"https://vtechworks.lib.vt.edu/oai/request"},"display":{"title":"Exploring a Novel Anti-Gonococcal Compound for Combating Drug-Resistant <i>Neisseria gonorrhoeae</i>","abstract":"The Gram-negative bacterium Neisseria gonorrhoeae, the causative agent of gonorrhea, is a significant public health concern due to its rapid development of resistance to antibiotics, leading to limited treatment options and potentially untreatable infections. This pathogen primarily infects the urogenital tract, but it can also affect the rectum, throat, and eyes, resulting in severe complications such as pelvic inflammatory disease and infertility if untreated. The rise in antibiotic-resistant gonorrhea underscores the urgent need for new therapeutics. To address this, suitable strains of N. gonorrhoeae for in vivo study were constructed. N. gonorrhoeae FA1090 is used in the mouse model of gonococcal infection due to its streptomycin resistance, which allows colonization. However, it is unsuitable for testing novel agents against multidrug-resistant N. gonorrhoeae due to its antibiotic susceptibility. Therefore, streptomycin-resistant mutants of N. gonorrhoeae CDC-181 (azithromycin-resistant) and WHO-X (ceftriaxone-resistant) were developed to evaluate the activity of potential anti-N. gonorrhoeae compounds. These mutants, CDC-181-rpsLA128G and WHO-X-rpsLA128G, successfully colonized the genital tracts of mice, making them suitable models for testing new treatments. Additionally, using a drug repurposing strategy, we identified nitroxoline, an FDA-approved drug, as a promising anti-gonococcal agent. Nitroxoline showed strong activity against a range of multidrug-resistant N. gonorrhoeae strains, including ceftriaxone-resistant ones, with an MIC90 of 0.5 µg/mL. It eradicated N. gonorrhoeae within 12 hours and prevented the development of resistant mutants. Nitroxoline also effectively penetrated human cervical cells and eradicated intracellular N. gonorrhoeae while minimally affecting commensal vaginal flora. Its mechanism involves chelation with metal ions, particularly Fe3+ and Fe2+. In conclusion, the development of streptomycin-resistant N. gonorrhoeae mutants and the identification of nitroxoline as a potent anti-gonococcal agent represent significant progress in combating multidrug-resistant gonorrhea. These findings offer promising avenues for new anti-gonococcal treatments in an era of increasing antibiotic resistance.","abstract_html":"The Gram-negative bacterium Neisseria gonorrhoeae, the causative agent of gonorrhea, is a significant public health concern due to its rapid development of resistance to antibiotics, leading to limited treatment options and potentially untreatable infections. This pathogen primarily infects the urogenital tract, but it can also affect the rectum, throat, and eyes, resulting in severe complications such as pelvic inflammatory disease and infertility if untreated. The rise in antibiotic-resistant gonorrhea underscores the urgent need for new therapeutics. To address this, suitable strains of N. gonorrhoeae for in vivo study were constructed. N. gonorrhoeae FA1090 is used in the mouse model of gonococcal infection due to its streptomycin resistance, which allows colonization. However, it is unsuitable for testing novel agents against multidrug-resistant N. gonorrhoeae due to its antibiotic susceptibility. Therefore, streptomycin-resistant mutants of N. gonorrhoeae CDC-181 (azithromycin-resistant) and WHO-X (ceftriaxone-resistant) were developed to evaluate the activity of potential anti-N. gonorrhoeae compounds. These mutants, CDC-181-rpsLA128G and WHO-X-rpsLA128G, successfully colonized the genital tracts of mice, making them suitable models for testing new treatments. Additionally, using a drug repurposing strategy, we identified nitroxoline, an FDA-approved drug, as a promising anti-gonococcal agent. Nitroxoline showed strong activity against a range of multidrug-resistant N. gonorrhoeae strains, including ceftriaxone-resistant ones, with an MIC90 of 0.5 µg/mL. It eradicated N. gonorrhoeae within 12 hours and prevented the development of resistant mutants. Nitroxoline also effectively penetrated human cervical cells and eradicated intracellular N. gonorrhoeae while minimally affecting commensal vaginal flora. Its mechanism involves chelation with metal ions, particularly Fe3+ and Fe2+. In conclusion, the development of streptomycin-resistant N. gonorrhoeae mutants and the identification of nitroxoline as a potent anti-gonococcal agent represent significant progress in combating multidrug-resistant gonorrhea. These findings offer promising avenues for new anti-gonococcal treatments in an era of increasing antibiotic resistance.","abstract_has_math":false,"creators":["Kikiowo, Babatomiwa"],"institution":"Virginia Tech","degree_name":"Master of Science","degree_level":"masters","degree_discipline":"Biomedical and Veterinary Sciences","degree_department":null,"school":null,"contributors":[],"advisors":[],"committee_chairs":["Seleem, Mohamed N."],"committee_members":["Lowell, Andrew N.","Mevers, Emily","Yang, Zhaomin"],"year":2024,"date_issued":"2024-08-21","date_published":"2024-08-21","updated_at":"2026-07-22T22:20:11Z","subjects":["Neisseria gonorrhoeae","gonococcal mouse model","antibiotic resistance","allelic exchange","gonorrhea"],"languages":["en"],"rights":["In Copyright"],"rights_urls":["http://rightsstatements.org/vocab/InC/1.0/"],"identifier_entries":[]},"links":{"outbound_url":"https://hdl.handle.net/10919/121112","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.committeechair","label":"Committee Chair","values":["Seleem, Mohamed N."]},{"key":"dc:contributor.committeemember","label":"Committee Member","values":["Lowell, Andrew N.","Mevers, Emily","Yang, Zhaomin"]},{"key":"dc:creator","label":"Author","values":["Kikiowo, Babatomiwa"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2024-09-11T12:39:58Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2024-09-11T12:39:58Z"]},{"key":"dc:date.issued","label":"Date","values":["2024-08-21"]},{"key":"dc:publisher","label":"Institution","values":["Virginia Tech"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]},{"key":"dc:type.dcmitype","label":"Dc Type Dcmitype","values":["Text"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Biomedical and Veterinary Sciences"]},{"key":"thesis:degree_level","label":"Degree Level","values":["masters"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Master of Science"]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["Virginia Polytechnic Institute and State University"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Neisseria gonorrhoeae","gonococcal mouse model","antibiotic resistance","allelic exchange","gonorrhea"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language.iso","label":"Language (ISO)","values":["en"]},{"key":"dc:rights","label":"Dc Rights","values":["In Copyright"]},{"key":"dc:rights.uri","label":"Rights URI","values":["http://rightsstatements.org/vocab/InC/1.0/"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://hdl.handle.net/10919/121112"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["The Gram-negative bacterium Neisseria gonorrhoeae, the causative agent of gonorrhea, is a significant public health concern due to its rapid development of resistance to antibiotics, leading to limited treatment options and potentially untreatable infections. This pathogen primarily infects the urogenital tract, but it can also affect the rectum, throat, and eyes, resulting in severe complications such as pelvic inflammatory disease and infertility if untreated. The rise in antibiotic-resistant gonorrhea underscores the urgent need for new therapeutics. To address this, suitable strains of N. gonorrhoeae for in vivo study were constructed. N. gonorrhoeae FA1090 is used in the mouse model of gonococcal infection due to its streptomycin resistance, which allows colonization. However, it is unsuitable for testing novel agents against multidrug-resistant N. gonorrhoeae due to its antibiotic susceptibility. Therefore, streptomycin-resistant mutants of N. gonorrhoeae CDC-181 (azithromycin-resistant) and WHO-X (ceftriaxone-resistant) were developed to evaluate the activity of potential anti-N. gonorrhoeae compounds. These mutants, CDC-181-rpsLA128G and WHO-X-rpsLA128G, successfully colonized the genital tracts of mice, making them suitable models for testing new treatments. Additionally, using a drug repurposing strategy, we identified nitroxoline, an FDA-approved drug, as a promising anti-gonococcal agent. Nitroxoline showed strong activity against a range of multidrug-resistant N. gonorrhoeae strains, including ceftriaxone-resistant ones, with an MIC90 of 0.5 µg/mL. It eradicated N. gonorrhoeae within 12 hours and prevented the development of resistant mutants. Nitroxoline also effectively penetrated human cervical cells and eradicated intracellular N. gonorrhoeae while minimally affecting commensal vaginal flora. Its mechanism involves chelation with metal ions, particularly Fe3+ and Fe2+. In conclusion, the development of streptomycin-resistant N. gonorrhoeae mutants and the identification of nitroxoline as a potent anti-gonococcal agent represent significant progress in combating multidrug-resistant gonorrhea. These findings offer promising avenues for new anti-gonococcal treatments in an era of increasing antibiotic resistance."]},{"key":"dc:description.abstractgeneral","label":"General Abstract","values":["Gonorrhea, caused by the bacterium Neisseria gonorrhoeae, is becoming increasingly difficult to treat because the bacteria has progressively developed resistance to antibiotics. This makes it challenging to find effective treatments and can lead to serious health issues like pelvic inflammatory disease and infertility if left untreated. The rise in antibiotic-resistant gonorrhea highlights the urgent need for new medications. N. gonorrhoeae FA1090 is used in the mouse model of gonococcal infection due to its streptomycin resistance, which allows colonization. However, it is unsuitable for testing novel agents against multidrug-resistant N. gonorrhoeae due to its antibiotic susceptibility. To address this, new strains of N. gonorrhoeae that are resistant to the antibiotic streptomycin were developed, which could be utilized to test the efficacy of potential novel treatments in the mouse model. These strains were able to successfully colonize the genital tracts of the mice, making them valuable models for studying new drugs. In addition to creating these new bacterial strains, nitroxoline, an FDA-approved drug, was identified as a potential therapeutic. Nitroxoline was effective against many strains of N. gonorrhoeae, including those resistant to the commonly used antibiotic ceftriaxone. It killed the bacteria within 12 hours and did not lead to the development of resistant mutants. Nitroxoline was also able to gain access into the human endocervical cells and clear the bacterial burden inside, while having minimal impact on the beneficial vaginal bacteria. Its effectiveness is mediated by to its ability to bind with metal ions. In conclusion, the development of these new bacterial strains and the discovery of nitroxoline as a promising treatment represent significant progress in the fight against drug-resistant gonorrhea. These findings offer hope for new, effective treatments in an era of increasing antibiotic resistance."]},{"key":"dc:description.degree","label":"Dc Description Degree","values":["Master of Science"]},{"key":"dc:format.medium","label":"Dc Format Medium","values":["ETD"]},{"key":"dc:format.mimetype","label":"Dc Format Mimetype","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Exploring a Novel Anti-Gonococcal Compound for Combating Drug-Resistant <i>Neisseria gonorrhoeae</i>"]}]}],"canonical_facts":{"dc:contributor.committeechair":["Seleem, Mohamed N."],"dc:contributor.committeemember":["Lowell, Andrew N.","Mevers, Emily","Yang, Zhaomin"],"dc:creator":["Kikiowo, Babatomiwa"],"dc:date.accessioned":["2024-09-11T12:39:58Z"],"dc:date.available":["2024-09-11T12:39:58Z"],"dc:date.issued":["2024-08-21"],"dc:description.abstract":["The Gram-negative bacterium Neisseria gonorrhoeae, the causative agent of gonorrhea, is a significant public health concern due to its rapid development of resistance to antibiotics, leading to limited treatment options and potentially untreatable infections. This pathogen primarily infects the urogenital tract, but it can also affect the rectum, throat, and eyes, resulting in severe complications such as pelvic inflammatory disease and infertility if untreated. The rise in antibiotic-resistant gonorrhea underscores the urgent need for new therapeutics. To address this, suitable strains of N. gonorrhoeae for in vivo study were constructed. N. gonorrhoeae FA1090 is used in the mouse model of gonococcal infection due to its streptomycin resistance, which allows colonization. However, it is unsuitable for testing novel agents against multidrug-resistant N. gonorrhoeae due to its antibiotic susceptibility. Therefore, streptomycin-resistant mutants of N. gonorrhoeae CDC-181 (azithromycin-resistant) and WHO-X (ceftriaxone-resistant) were developed to evaluate the activity of potential anti-N. gonorrhoeae compounds. These mutants, CDC-181-rpsLA128G and WHO-X-rpsLA128G, successfully colonized the genital tracts of mice, making them suitable models for testing new treatments. Additionally, using a drug repurposing strategy, we identified nitroxoline, an FDA-approved drug, as a promising anti-gonococcal agent. Nitroxoline showed strong activity against a range of multidrug-resistant N. gonorrhoeae strains, including ceftriaxone-resistant ones, with an MIC90 of 0.5 µg/mL. It eradicated N. gonorrhoeae within 12 hours and prevented the development of resistant mutants. Nitroxoline also effectively penetrated human cervical cells and eradicated intracellular N. gonorrhoeae while minimally affecting commensal vaginal flora. Its mechanism involves chelation with metal ions, particularly Fe3+ and Fe2+. In conclusion, the development of streptomycin-resistant N. gonorrhoeae mutants and the identification of nitroxoline as a potent anti-gonococcal agent represent significant progress in combating multidrug-resistant gonorrhea. These findings offer promising avenues for new anti-gonococcal treatments in an era of increasing antibiotic resistance."],"dc:description.abstractgeneral":["Gonorrhea, caused by the bacterium Neisseria gonorrhoeae, is becoming increasingly difficult to treat because the bacteria has progressively developed resistance to antibiotics. This makes it challenging to find effective treatments and can lead to serious health issues like pelvic inflammatory disease and infertility if left untreated. The rise in antibiotic-resistant gonorrhea highlights the urgent need for new medications. N. gonorrhoeae FA1090 is used in the mouse model of gonococcal infection due to its streptomycin resistance, which allows colonization. However, it is unsuitable for testing novel agents against multidrug-resistant N. gonorrhoeae due to its antibiotic susceptibility. To address this, new strains of N. gonorrhoeae that are resistant to the antibiotic streptomycin were developed, which could be utilized to test the efficacy of potential novel treatments in the mouse model. These strains were able to successfully colonize the genital tracts of the mice, making them valuable models for studying new drugs. In addition to creating these new bacterial strains, nitroxoline, an FDA-approved drug, was identified as a potential therapeutic. Nitroxoline was effective against many strains of N. gonorrhoeae, including those resistant to the commonly used antibiotic ceftriaxone. It killed the bacteria within 12 hours and did not lead to the development of resistant mutants. Nitroxoline was also able to gain access into the human endocervical cells and clear the bacterial burden inside, while having minimal impact on the beneficial vaginal bacteria. Its effectiveness is mediated by to its ability to bind with metal ions. In conclusion, the development of these new bacterial strains and the discovery of nitroxoline as a promising treatment represent significant progress in the fight against drug-resistant gonorrhea. These findings offer hope for new, effective treatments in an era of increasing antibiotic resistance."],"dc:description.degree":["Master of Science"],"dc:format.medium":["ETD"],"dc:format.mimetype":["application/pdf"],"dc:identifier.uri":["https://hdl.handle.net/10919/121112"],"dc:language.iso":["en"],"dc:publisher":["Virginia Tech"],"dc:rights":["In Copyright"],"dc:rights.uri":["http://rightsstatements.org/vocab/InC/1.0/"],"dc:subject":["Neisseria gonorrhoeae","gonococcal mouse model","antibiotic resistance","allelic exchange","gonorrhea"],"dc:title":["Exploring a Novel Anti-Gonococcal Compound for Combating Drug-Resistant <i>Neisseria gonorrhoeae</i>"],"dc:type":["Thesis"],"dc:type.dcmitype":["Text"],"thesis:degree_discipline":["Biomedical and Veterinary Sciences"],"thesis:degree_level":["masters"],"thesis:degree_name":["Master of Science"],"thesis:institution_name":["Virginia Polytechnic Institute and State University"]},"updated_at":"2026-07-22T22:20:11Z"}