{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T09:40:27Z","timestamp":1785404427344,"version":"3.56.0"},"reference-count":74,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T00:00:00Z","timestamp":1781654400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["UID\/04413\/2025"],"award-info":[{"award-number":["UID\/04413\/2025"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["LA\/P\/0117\/2020"],"award-info":[{"award-number":["LA\/P\/0117\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"award":["UID\/04413\/2025"],"award-info":[{"award-number":["UID\/04413\/2025"]}],"id":[{"id":"https:\/\/ror.org\/00snfqn58","id-type":"ROR","asserted-by":"publisher"}]},{"award":["LA\/P\/0117\/2020"],"award-info":[{"award-number":["LA\/P\/0117\/2020"]}],"id":[{"id":"https:\/\/ror.org\/00snfqn58","id-type":"ROR","asserted-by":"publisher"}]},{"name":"DrugsForNg project","award":["UID\/04413\/2020"],"award-info":[{"award-number":["UID\/04413\/2020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Background\/Objectives: Neisseria gonorrhoeae is a high-priority pathogen for the development of new therapeutic alternatives. Efflux pumps are attractive drug targets because their inactivation influences N. gonorrhoeae susceptibility to multiple antimicrobials. Since most gonococcal efflux systems are energy-dependent, interference with energy metabolism and membrane transport may indirectly compromise efflux activity. Efflux inhibitors may increase intracellular antibiotic concentration, although this requires validation in resistant strains. The most effective efflux inhibitors interfere with energy metabolism, affecting several physiological processes, including efflux. In this work, we used an in silico drug repurposing strategy targeting proteins involved in membrane transport and energy metabolism in N. gonorrhoeae. A subset of candidate drugs were subsequently evaluated in vitro using only the reference strain N. gonorrhoeae ATCC 49226. Methods: Predicted drug\u2013target interactions were identified using publicly available databases such as DrugBank and STITCH. Minimum inhibitory concentrations (MICs) of selected drugs against N. gonorrhoeae were determined by microdilution. Changes in intracellular ethidium bromide accumulation were assessed by real-time fluorometry as an indirect indicator of possible efflux-related interference. Results: In silico analysis identified 32 predicted targets associated with 57 approved drugs. Triclabendazole and dequalinium showed the lowest MIC values of the tested compounds (2 and 4 mg\/L, respectively). Ketotifen and verapamil demonstrated activity consistent with possible efflux interference, as indicated by increased ethidium bromide accumulation. Atovaquone showed adjuvant-like effects in combination assays, suggesting that mechanisms other than efflux-related interference may contribute to its activity. Conclusions: Overall, this preliminary study identifies approved drugs with antimicrobial or adjuvant activity against a single N. gonorrhoeae reference strain, supporting further investigation in clinically relevant and efflux-variant strains.<\/jats:p>","DOI":"10.3390\/antibiotics15060616","type":"journal-article","created":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T08:22:56Z","timestamp":1781684576000},"page":"616","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Targeting Membrane Transport and Energy Metabolism for the Identification of Repurposed Drug Candidates Against Neisseria gonorrhoeae Using an In Silico Strategy"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-2206-4138","authenticated-orcid":false,"given":"In\u00eas","family":"Pereira","sequence":"first","affiliation":[{"name":"Global Health and Tropical Medicine, GHTM, LA-REAL, Instituto de Higiene e Medicina Tropical, IHMT, Universidade NOVA de Lisboa, 1349-008 Lisboa, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9","family":"Pina","sequence":"additional","affiliation":[{"name":"Global Health and Tropical Medicine, GHTM, LA-REAL, Instituto de Higiene e Medicina Tropical, IHMT, Universidade NOVA de Lisboa, 1349-008 Lisboa, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-5003-1001","authenticated-orcid":false,"given":"In\u00eas","family":"V\u00edtor","sequence":"additional","affiliation":[{"name":"Global Health and Tropical Medicine, GHTM, LA-REAL, Instituto de Higiene e Medicina Tropical, IHMT, Universidade NOVA de Lisboa, 1349-008 Lisboa, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatriz","family":"Santos","sequence":"additional","affiliation":[{"name":"Global Health and Tropical Medicine, GHTM, LA-REAL, Instituto de Higiene e Medicina Tropical, IHMT, Universidade NOVA de Lisboa, 1349-008 Lisboa, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Henriques","sequence":"additional","affiliation":[{"name":"Global Health and Tropical Medicine, GHTM, LA-REAL, Instituto de Higiene e Medicina Tropical, IHMT, Universidade NOVA de Lisboa, 1349-008 Lisboa, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3536-2733","authenticated-orcid":false,"given":"Isabel","family":"Couto","sequence":"additional","affiliation":[{"name":"Global Health and Tropical Medicine, GHTM, LA-REAL, Instituto de Higiene e Medicina Tropical, IHMT, Universidade NOVA de Lisboa, 1349-008 Lisboa, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3421-7833","authenticated-orcid":false,"given":"Filomena M.","family":"Pereira","sequence":"additional","affiliation":[{"name":"Global Health and Tropical Medicine, GHTM, LA-REAL, Instituto de Higiene e Medicina Tropical, IHMT, Universidade NOVA de Lisboa, 1349-008 Lisboa, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9676-6251","authenticated-orcid":false,"given":"Miguel","family":"Viveiros","sequence":"additional","affiliation":[{"name":"Global Health and Tropical Medicine, GHTM, LA-REAL, Instituto de Higiene e Medicina Tropical, IHMT, Universidade NOVA de Lisboa, 1349-008 Lisboa, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5066-9982","authenticated-orcid":false,"given":"Ana","family":"Armada","sequence":"additional","affiliation":[{"name":"Global Health and Tropical Medicine, GHTM, LA-REAL, Instituto de Higiene e Medicina Tropical, IHMT, Universidade NOVA de Lisboa, 1349-008 Lisboa, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4096-2410","authenticated-orcid":false,"given":"Sofia Santos","family":"Costa","sequence":"additional","affiliation":[{"name":"Global Health and Tropical Medicine, GHTM, LA-REAL, Instituto de Higiene e Medicina Tropical, IHMT, Universidade NOVA de Lisboa, 1349-008 Lisboa, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liliana","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"Global Health and Tropical Medicine, GHTM, LA-REAL, Instituto de Higiene e Medicina Tropical, IHMT, Universidade NOVA de Lisboa, 1349-008 Lisboa, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1016\/S0140-6736(24)01867-1","article-title":"Global Burden of Bacterial Antimicrobial Resistance 1990\u20132021: A Systematic Analysis with Forecasts to 2050","volume":"404","author":"Naghavi","year":"2024","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1016\/S1473-3099(17)30753-3","article-title":"Discovery, Research, and Development of New Antibiotics: The WHO Priority List of Antibiotic-Resistant Bacteria and Tuberculosis","volume":"18","author":"Tacconelli","year":"2018","journal-title":"Lancet Infect. Dis."},{"key":"ref_3","unstructured":"European Centre for Disease Prevention and Control (2026, January 09). Gonorrhoea-Annual Epidemiological Report for 2023 [Internet]. Stockholm; Report. Available online: https:\/\/www.ecdc.europa.eu\/en\/publications-data\/gonorrhoea-annual-epidemiological-report-2023."},{"key":"ref_4","unstructured":"Centers for Disease Control and Prevention (2026, January 09). Sexually Transmitted Infections Surveillance, 2024 (Provisional)|STI Statistics|CDC [Internet]. Report, Available online: https:\/\/www.cdc.gov\/sti-statistics\/annual\/index.html."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"101318","DOI":"10.1016\/j.lanepe.2025.101318","article-title":"Antimicrobial Resistance in Neisseria gonorrhoeae and Its Risk Groups in 23 European Countries in 2022 Within the European Gonococcal Antimicrobial Surveillance Programme (Euro-GASP): A Retrospective Observational Study","volume":"54","author":"Jacobsson","year":"2025","journal-title":"Lancet Reg. Health Eur."},{"key":"ref_6","unstructured":"European Centre for Disease Prevention and Control (ECDC) (2024). Gonococcal Antimicrobial Susceptibility Surveillance in the EU\/EEA, ECDC. Available online: https:\/\/www.ecdc.europa.eu\/en\/publications-data\/gonococcal-antimicrobial-susceptibility-surveillance-eu-eea."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1071\/SH19034","article-title":"New Treatment Options for Neisseria gonorrhoeae in the Era of Emerging Antimicrobial Resistance","volume":"16","author":"Lewis","year":"2019","journal-title":"Sex. Health"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.1093\/cid\/ciae386","article-title":"US Food and Drug Administration, Centers for Disease Control and Prevention, and National Institutes of Health Co-Sponsored Public Workshop Summary\u2014Development Considerations of Antimicrobial Drugs for the Treatment of Gonorrhea","volume":"81","author":"Hiruy","year":"2026","journal-title":"Clin. Infect. Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/S0140-6736(25)01953-1","article-title":"Zoliflodacin Versus Ceftriaxone Plus Azithromycin for Treatment of Uncomplicated Urogenital Gonorrhoea: An International, Randomised, Controlled, Open-Label, Phase 3, Non-Inferiority Clinical Trial","volume":"407","author":"Luckey","year":"2026","journal-title":"Lancet"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1608","DOI":"10.1016\/S0140-6736(25)00628-2","article-title":"Oral Gepotidacin for the Treatment of Uncomplicated Urogenital Gonorrhoea (EAGLE-1): A Phase 3 Randomised, Open-Label, Non-Inferiority, Multicentre Study","volume":"405","author":"Ross","year":"2025","journal-title":"Lancet"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3029","DOI":"10.1093\/jac\/dkae327","article-title":"Neisseria gonorrhoeae Treatment Failure to the Recommended Antibiotic Regimen-Qu\u00e9bec, Canada, 2015-19","volume":"79","author":"Blouin","year":"2024","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e532","DOI":"10.1016\/S1473-3099(24)00001-X","article-title":"Managing Treatment Failure in Neisseria gonorrhoeae Infection: Current Guidelines and Future Directions","volume":"24","author":"Fifer","year":"2024","journal-title":"Lancet Infect. Dis."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3556","DOI":"10.1128\/AAC.00038-14","article-title":"Importance of Multidrug Efflux Pumps in the Antimicrobial Resistance Property of Clinical Multidrug-Resistant Isolates of Neisseria gonorrhoeae","volume":"58","author":"Golparian","year":"2014","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e01576-19","DOI":"10.1128\/mBio.01576-19","article-title":"Could Dampening Expression of the Neisseria gonorrhoeae mtrCDE-Encoded Efflux Pump Be a Strategy To Preserve Currently or Resurrect Formerly Used Antibiotics To Treat Gonorrhea?","volume":"10","author":"Chen","year":"2019","journal-title":"mBio"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e0154221","DOI":"10.1128\/AAC.01542-21","article-title":"Self-Inhibitory Peptides Targeting the Neisseria gonorrhoeae MtrCDE Efflux Pump Increase Antibiotic Susceptibility","volume":"66","author":"Evert","year":"2022","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"856","DOI":"10.1093\/jac\/dki333","article-title":"Characterization of the MacA-MacB Efflux System in Neisseria gonorrhoeae","volume":"56","author":"Balthazar","year":"2005","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1128\/JB.185.3.1101-1106.2003","article-title":"The NorM Efflux Pump of Neisseria gonorrhoeae and Neisseria meningitidis Recognizes Antimicrobial Cationic Compounds","volume":"185","author":"Dunham","year":"2003","journal-title":"J. Bacteriol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.celrep.2015.03.003","article-title":"Structure and Function of Neisseria gonorrhoeae MtrF Iluminates a Class of Antimetabolite Efflux Pumps","volume":"11","author":"Su","year":"2015","journal-title":"Cell Rep."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Li, X.Z., Elkins, C., and Zgurskaya, H. (2016). Efflux Pumps in Neisseria gonorrhoeae: Contributions to Antimicrobial Resistance and Virulence. Efflux-Mediated Antimicrobial Resistance in Bacteria, Springer International Publishing.","DOI":"10.1007\/978-3-319-39658-3"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e01340-20","DOI":"10.1128\/mBio.01340-20","article-title":"New Multidrug Efflux Inhibitors for Gram-Negative Bacteria","volume":"11","author":"Marshall","year":"2020","journal-title":"mBio"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1080\/14787210.2020.1760845","article-title":"Efflux Pump Inhibitors as a Promising Adjunct Therapy Against Drug Resistant Tuberculosis: A New Strategy to Revisit Mycobacterial Targets and Repurpose Old Drugs","volume":"18","author":"Rodrigues","year":"2020","journal-title":"Expert Rev. Anti. Infect. Ther."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"4548","DOI":"10.1073\/pnas.0500469102","article-title":"Inhibitors of Type II NADH:Menaquinone Oxidoreductase Represent a Class of Antitubercular Drugs","volume":"102","author":"Weinstein","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e02107\u201317","DOI":"10.1128\/AAC.02107-17","article-title":"Verapamil Targets Membrane Energetics in Mycobacterium tuberculosis","volume":"62","author":"Chen","year":"2018","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1128\/CMR.00117-14","article-title":"The Challenge of Efflux-Mediated Antibiotic Resistance in Gram-negative Bacteria","volume":"28","author":"Li","year":"2015","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1111\/jphp.13273","article-title":"Drug Repositioning: A Brief Overview","volume":"72","author":"Jourdan","year":"2020","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1111\/apm.13014","article-title":"The First Wide-Scale Drug Repurposing Screen Using the Prestwick Chemical Library (1200 Bioactive Molecules) Against Neisseria gonorrhoeae Identifies High In Vitro Activity of Auranofin and Many Additional Drugs","volume":"128","author":"Foerster","year":"2020","journal-title":"APMIS"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e02206\u201319","DOI":"10.1128\/AAC.02206-19","article-title":"Repurposing Fenamic Acid Drugs To Combat Multidrug-Resistant Neisseria gonorrhoeae","volume":"64","author":"Seong","year":"2020","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Bispo, N.A., Culleton, R., Silva, L.A., and Cravo, P. (2013). A Systematic In Silico Search for Target Similarity Identifies Several Approved Drugs with Potential Activity against the Plasmodium falciparum Apicoplast. PLoS ONE, 8.","DOI":"10.1371\/annotation\/0bbd3579-5212-4dcf-a5ef-dd3d8e26f287"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Neves, B.J., Braga, R.C., Bezerra, J.C.B., Cravo, P.V.L., and Andrade, C.H. (2015). In Silico Repositioning-Chemogenomics Strategy Identifies New Drugs with Potential Activity against Multiple Life Stages of Schistosoma mansoni. PLoS Negl. Trop. Dis., 9.","DOI":"10.1371\/journal.pntd.0003435"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1093\/nar\/28.1.27","article-title":"KEGG: Kyoto Encyclopedia of Genes and Genomes","volume":"28","author":"Kanehisa","year":"2000","journal-title":"Nucleic Acids Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"D523","DOI":"10.1093\/nar\/gkac1052","article-title":"UniProt: The Universal Protein Knowledgebase in 2023","volume":"51","author":"Bateman","year":"2023","journal-title":"Nucleic Acids Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"D1074","DOI":"10.1093\/nar\/gkx1037","article-title":"DrugBank 5.0: A Major Update to the DrugBank Database for 2018","volume":"46","author":"Wishart","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"D380","DOI":"10.1093\/nar\/gkv1277","article-title":"STITCH 5: Augmenting Protein-Chemical Iteraction Networks with Tissue and Affinity Data","volume":"44","author":"Szklarczyk","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"W344","DOI":"10.1093\/nar\/gkw408","article-title":"ConSurf 2016: An Improved Methodology to Estimate and Visualize Evolutionary Conservation in Macromolecules","volume":"44","author":"Ashkenazy","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"D29","DOI":"10.1093\/nar\/gkac1032","article-title":"Database Resources of the National Center for Biotechnology Information in 2023","volume":"51","author":"Sayers","year":"2023","journal-title":"Nucleic Acids Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1969","DOI":"10.1021\/acsinfecdis.1c00055","article-title":"Structure-Activity Relationship Studies of Acetazolamide-Based Carbonic Anhydrase Inhibitors with Activity against Neisseria gonorrhoeae","volume":"7","author":"Hewitt","year":"2021","journal-title":"ACS Infect. Dis."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"105454","DOI":"10.1016\/j.micpath.2022.105454","article-title":"In Vivo Efficacy of Acetazolamide in a Mouse Model of Neisseria gonorrhoeae Infection","volume":"164","author":"Abutaleb","year":"2022","journal-title":"Microb. Pathog."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1016\/S0140-6736(00)41665-X","article-title":"Sulphanilamide in gonorrhoea: An analysis of 633 cases","volume":"232","author":"Cokkinis","year":"1938","journal-title":"Lancet"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1097\/00007435-198304000-00007","article-title":"Introduction of Sulfonamide Therapy for Gonorrhea","volume":"10","author":"Kampmeier","year":"1983","journal-title":"Sex. Transm. Dis."},{"key":"ref_40","first-page":"302","article-title":"Single Dose Ciprofloxacin for Treating Gonococcal Infections in Men","volume":"61","author":"Loo","year":"1985","journal-title":"Genitourin. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2569","DOI":"10.1093\/jac\/dkab217","article-title":"Identification of Bile Acid and Fatty Acid Species as Candidate Rapidly Bactericidal Agents for Topical Treatment of Gonorrhoea","volume":"76","author":"Palace","year":"2021","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"e02277\u201319","DOI":"10.1128\/mBio.02277-19","article-title":"Multidrug Resistance in Neisseria gonorrhoeae: Identification of Functionally Important Residues in the MtrD Efflux Protein","volume":"10","author":"Chitsaz","year":"2019","journal-title":"mBio"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Pi, H., Ogunniyi, A.D., Savaliya, B., Nguyen, H.T., Page, S.W., Lacey, E., Venter, H., and Trott, D.J. (2021). Repurposing of the Fasciolicide Triclabendazole to Treat Infections Caused by Staphylococcus spp. and Vancomycin-Resistant Enterococci. Microorganisms, 9.","DOI":"10.3390\/microorganisms9081697"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1128\/AAC.25.3.375","article-title":"Susceptibilities of Bacterial and Fungal Urinary Tract Isolates to Desferrioxamine","volume":"25","author":"Lowy","year":"1984","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"e01454\u201317","DOI":"10.1128\/AAC.01454-17","article-title":"In Vitro Antibacterial Properties of Cefiderocol, a Novel Siderophore Cephalosporin, against Gram-Negative Bacteria","volume":"62","author":"Ito","year":"2017","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"5602","DOI":"10.1038\/s41598-020-62696-3","article-title":"Investigation of Auranofin and Gold-Containing Analogues Antibacterial Activity Against Mltidrug-Resistant Neisseria gonorrhoeae","volume":"10","author":"Elkashif","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Elhassanny, A.E.M., Abutaleb, N.S., and Seleem, M.N. (2022). Auranofin Exerts Antibacterial Activity Against Neisseria gonorrhoeae in a Female Mouse Model of Genital Tract Infection. PLoS ONE, 17.","DOI":"10.1371\/journal.pone.0266764"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2101","DOI":"10.1016\/0006-2952(84)90579-3","article-title":"Kinetics of Methotrexate Binding to Dihydrofolate Reductase from Neisseria gonorrhoeae","volume":"33","author":"Baccanari","year":"1984","journal-title":"Biochem. Pharmacol."},{"key":"ref_49","unstructured":"Clinical and Laboratory Standards Institute (CLSI) (2023). Performance Standards for Antimicrobial Susceptibility Testing, CLSI. [33rd ed.]."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1089\/adt.2016.752","article-title":"An Experimental Model for the Rapid Screening of Compounds with Potential Use Against Mycobacteria","volume":"14","author":"Costa","year":"2016","journal-title":"Assay Drug Dev. Technol."},{"key":"ref_51","unstructured":"European Centre for Disease Prevention and Control (2026, January 08). Response Plan to Control and Manage the Threat of Multi-and Extensively Drug-Resistant Gonorrhoea in Europe-2019 Update [Internet]. Stockholm; Report. Available online: https:\/\/www.ecdc.europa.eu\/en\/publications-data\/response-plan-control-and-manage-threat-multi-and-extensively-drug-resistant-0."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1186\/1754-1611-3-18","article-title":"Fluorometric Determination of Ethidium Bromide Efflux Kinetics in Escherichia coli","volume":"3","author":"Rodrigues","year":"2009","journal-title":"J. Biol. Eng."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1007\/978-1-0716-1460-0_9","article-title":"Measuring Efflux and Permeability in Mycobacteria","volume":"2314","author":"Rodrigues","year":"2021","journal-title":"Methods Mol. Biol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1038\/s41572-019-0128-6","article-title":"Gonorrhoea","volume":"5","author":"Unemo","year":"2019","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_55","first-page":"651","article-title":"Drug Discovery and Development: Role of Basic Biological Research","volume":"3","author":"Mohs","year":"2017","journal-title":"Alzheimers Dement."},{"key":"ref_56","first-page":"89","article-title":"Modern Drug Discovery Process: An In Silico Approach","volume":"2","author":"Rao","year":"2011","journal-title":"J. Bioinform. Seq. Anal."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"114467","DOI":"10.1016\/j.bcp.2021.114467","article-title":"Medicinal Applications and Molecular Targets of Dequalinium Chloride","volume":"186","author":"Bailly","year":"2021","journal-title":"Biochem. Pharmacol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1007\/s11096-006-9069-8","article-title":"Effect of Fascioliasis on the Pharmacokinetic Parameters of Triclabendazole in Human Subjects","volume":"29","author":"Salem","year":"2007","journal-title":"Pharm. World Sci."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"27458","DOI":"10.1074\/jbc.M502319200","article-title":"Uncovering the Molecular Mode of Action of the Antimalarial Drug Atovaquone Using a Bacterial System","volume":"280","author":"Mather","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2935","DOI":"10.1002\/1873-3468.13868","article-title":"The Cytochrome bc1 Complex as an Antipathogenic Target","volume":"594","author":"Fisher","year":"2020","journal-title":"FEBS Lett."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2395","DOI":"10.1128\/JB.00002-10","article-title":"Organization of the Electron Transfer Chain to Oxygen in the Obligate Human Pathogen Neisseria gonorrhoeae: Roles for Cytochromes c4 and c5, But Not Cytochrome c2, in Oxygen Reduction","volume":"192","author":"Li","year":"2010","journal-title":"J. Bacteriol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1159\/000315101","article-title":"Functional Inhibitors of Acid Sphingomyelinase (FIASMAs): A Novel Pharmacological Group of Drugs with Broad Clinical applications","volume":"26","author":"Kornhuber","year":"2010","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1016\/S0092-8674(00)80448-1","article-title":"Acidic Sphingomyelinase Mediates Entry of N. gonorrhoeae into Nonphagocytic Cells","volume":"91","author":"Gulbins","year":"1997","journal-title":"Cell"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1016\/j.anai.2013.10.003","article-title":"Ketotifen in the Management of Chronic Urticaria: Resurrection of an Od Drug","volume":"111","author":"Sokol","year":"2013","journal-title":"Ann. Allergy Asthma Immunol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1007\/s12639-014-0623-3","article-title":"The Inhibitory Effect of Cromolyn Sodium and Ketotifen on Toxoplasma gondii Entrance Into Host Cells In Vitro and In Vivo","volume":"40","author":"Rezaei","year":"2016","journal-title":"J. Parasit. Dis."},{"key":"ref_66","first-page":"e82389","article-title":"In Vitro Effects of Ketotifen and Cromolyn Sodium on Promastigotes and Amastigotes of Leishmania major","volume":"12","author":"Sarouey","year":"2019","journal-title":"Jundishapur J. Microbiol."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Endo, T.H., Santos, M.H.d.M., Scandorieiro, S., Gon\u00e7alves, B.C., Vespero, E.C., Perugini, M.R.E., Pavanelli, W.R., Nakazato, G., and Kobayashi, R.K.T. (2025). Selective Serotonin Reuptake Inhibitors: Antimicrobial Activity Against ESKAPEE Bacteria and Mechanisms of Action. Antibiotics, 14.","DOI":"10.3390\/antibiotics14010051"},{"key":"ref_68","first-page":"4","article-title":"Sertraline Enhances the Activity of Antimicrobial Agents Against Pathogens of Clinical Relevance","volume":"22","author":"Ayaz","year":"2015","journal-title":"J. Biol. Res."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"129","DOI":"10.4103\/ijmr.IJMR_2079_17","article-title":"Efflux Pump Inhibitors for Bacterial Pathogens: From Bench to Bedside","volume":"149","author":"Sharma","year":"2019","journal-title":"Indian J. Med. Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1128\/AAC.45.1.105-116.2001","article-title":"Identification and Characterization of Inhibitors of Multidrug Resistance Efflux Pumps in Pseudomonas aeruginosa: Novel Agents for Combination Therapy","volume":"45","author":"Lomovskaya","year":"2001","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"107682","DOI":"10.1016\/j.compbiolchem.2022.107682","article-title":"Identification of Novel Efflux Pump Inhibitors for Neisseria gonorrhoeae Via Multiple Ligand-Based Pharmacophores, E-pharmacophore, Molecular Docking, Density Functional Theory, and Molecular Dynamics Approaches","volume":"98","author":"Jain","year":"2022","journal-title":"Comput. Biol. Chem."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1067\/mcp.2000.110559","article-title":"Hypotensive Effect of Calcium Channel Blockers is Parallel with Carbonic Anhydrase I Inhibition","volume":"68","author":"Puscas","year":"2000","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"6035","DOI":"10.1128\/JB.00566-08","article-title":"Complete Genome Sequence of Neisseria gonorrhoeae NCCP11945","volume":"190","author":"Gyung","year":"2008","journal-title":"J. Bacteriol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1961","DOI":"10.1093\/jac\/dkx113","article-title":"A New Rapid Resazurin-Based Microdilution Assay for Antimicrobial Susceptibility Testing of Neisseria gonorrhoeae","volume":"72","author":"Foerster","year":"2017","journal-title":"J. Antimicrob. Chemother."}],"container-title":["Antibiotics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-6382\/15\/6\/616\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T07:18:57Z","timestamp":1782285537000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-6382\/15\/6\/616"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,17]]},"references-count":74,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["antibiotics15060616"],"URL":"https:\/\/doi.org\/10.3390\/antibiotics15060616","relation":{},"ISSN":["2079-6382"],"issn-type":[{"value":"2079-6382","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,17]]}}}