{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T15:09:03Z","timestamp":1778771343057,"version":"3.51.4"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T00:00:00Z","timestamp":1769644800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Tenovus Scotland","award":["S23-22"],"award-info":[{"award-number":["S23-22"]}]},{"name":"The Academy of Medical Sciences Springboard","award":["SBF008\\1043"],"award-info":[{"award-number":["SBF008\\1043"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,2,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>Bacterial vaginosis (BV) is the most common vaginal disorder in women of reproductive age. Current therapies are limited by poor activity against biofilms and high recurrence rates (&amp;gt;50%), demonstrating that new antimicrobials are required. Drug repurposing is an attractive approach for the discovery of new antimicrobials, so we aimed to screen repurposed libraries for activity against the key BV pathobiont Gardnerella vaginalis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>Two drug libraries from Medicines for Malaria Venture comprising 640 compounds were screened against G. vaginalis and various Lactobacilli species. Initial screening identified 16\u00a0G. vaginalis-selective compounds, of which 10 showed\u00a0\u226590% inhibition of planktonic growth while sparing Lactobacillus crispatus. Subsequent assays revealed that three candidates displayed activity against pre-formed G. vaginalis biofilms; MMV1634360 (an antiproliferative compound with reported anticancer and antifungal activity), MMV1582487 (originally developed as an Escherichia coli aminopeptidase N inhibitor), and MMV1582497 (a thymidylate kinase inhibitor developed for Mycobacterium tuberculosis). All three produced\u00a0&amp;gt;2-log reduction in viable cell counts at 10\u00a0\u00b5M (P\u00a0&amp;lt;\u00a00.05 for all compounds). Further cytotoxicity testing in VK2\/E6E7 vaginal epithelial cells excluded MMV1634360 and MMV1582497 due to off-target effects, leaving MMV1582487 as a leading candidate. MMV1582487 demonstrated further activity against a high biofilm-forming G. vaginalis clinical isolate with\u00a0&amp;gt;4log10 CFU\/ml reduction in viable cell counts at 10\u00a0\u00b5M (P\u00a0&amp;lt;\u00a00.001), and synergy with existing antibiotic therapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>We demonstrate that MMV1582487 is a selective, non-cytotoxic, anti-biofilm candidate against G. vaginalis, supporting its potential as a novel therapeutic option for BV.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jambio\/lxag034","type":"journal-article","created":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T12:41:28Z","timestamp":1769604088000},"source":"Crossref","is-referenced-by-count":0,"title":["Narrow-spectrum drug repurposing: targeting\n                    <i>Gardnerella vaginalis<\/i>\n                    biofilms associated with bacterial vaginosis"],"prefix":"10.1093","volume":"137","author":[{"given":"William","family":"Johnston","sequence":"first","affiliation":[{"name":"Department of Biological and Biomedical Sciences, Glasgow Caledonian University , Cowcaddens Road, Glasgow G4 0BA ,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jamie","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Biological and Biomedical Sciences, Glasgow Caledonian University , Cowcaddens Road, Glasgow G4 0BA ,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elisa","family":"Giammarini","sequence":"additional","affiliation":[{"name":"Department of Biological and Biomedical Sciences, Glasgow Caledonian University , Cowcaddens Road, Glasgow G4 0BA ,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amy","family":"Campbell","sequence":"additional","affiliation":[{"name":"Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde , 161 Cathedral St, Glasgow G4 0RE ,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anthony J","family":"Slate","sequence":"additional","affiliation":[{"name":"Department of Physical and Life Sciences, School of Applied Sciences, University of Huddersfield , Queensgate Campus, Huddersfield HD1 3DH ,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ermando","family":"Canga","sequence":"additional","affiliation":[{"name":"Department of Biosciences, Durham University , Stockton Road, Durham DH1 3LE ,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marino","family":"Swanzy-Krah","sequence":"additional","affiliation":[{"name":"Department of Biological and Biomedical Sciences, Glasgow Caledonian University , Cowcaddens Road, Glasgow G4 0BA ,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pranitha","family":"Murali","sequence":"additional","affiliation":[{"name":"Department of Biological and Biomedical Sciences, Glasgow Caledonian University , Cowcaddens Road, Glasgow G4 0BA ,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark","family":"Mason","sequence":"additional","affiliation":[{"name":"Sandyford Sexual Health Service, NHS Greater Glasgow and Clyde , 6 Sandyford Place, Glasgow G3 7NB ,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rebecca","family":"Metcalfe","sequence":"additional","affiliation":[{"name":"Sandyford Sexual Health Service, NHS Greater Glasgow and Clyde , 6 Sandyford Place, Glasgow G3 7NB ,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charlotte-Eve","family":"Short","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease, Imperial College London , South Kensington Campus, London SW7 2AZ ,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryan","family":"Kean","sequence":"additional","affiliation":[{"name":"Department of Biological and Biomedical Sciences, Glasgow Caledonian University , Cowcaddens Road, Glasgow G4 0BA ,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2026,1,29]]},"reference":[{"key":"2026051410074709300_bib1","doi-asserted-by":"publisher","first-page":"4030","DOI":"10.1021\/acsinfecdis.4c00700","article-title":"Global Health Priority Box\u2014proactive pandemic preparedness","volume":"10","author":"Adam","year":"2024","journal-title":"ACS Infect Dis"},{"key":"2026051410074709300_bib2","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1097\/01.JAA.0000526770.60197.fa","article-title":"Bacterial vaginosis: a practical review","volume":"30","author":"Bagnall","year":"2017","journal-title":"J Am Acad Physician Assist"},{"key":"2026051410074709300_bib3","doi-asserted-by":"publisher","first-page":"1478","DOI":"10.1086\/503780","article-title":"High recurrence rates of bacterial vaginosis over the course of 12 months after oral metronidazole therapy and factors associated with recurrence","volume":"193","author":"Bradshaw","year":"2006","journal-title":"J Infect Dis"},{"key":"2026051410074709300_bib4","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1038\/s41572-025-00626-1","article-title":"Bacterial vaginosis","volume":"11","author":"Bradshaw","year":"2025","journal-title":"Nat Rev Dis Primers"},{"key":"2026051410074709300_bib5","doi-asserted-by":"publisher","first-page":"224","DOI":"10.1097\/OLQ.0000000000001744","article-title":"Epidemiologic evidence on the role of Lactobacillus iners in sexually transmitted infections and bacterial vaginosis: a series of systematic reviews and meta-analyses","volume":"50","author":"Carter","year":"2023","journal-title":"Sexual Trans Dis"},{"key":"2026051410074709300_bib6","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1186\/s12934-020-01464-4","article-title":"Vaginal microbiota and the potential of Lactobacillus derivatives in maintaining vaginal health","volume":"19","author":"Chee","year":"2020","journal-title":"Microb Cell Fact"},{"key":"2026051410074709300_bib7","doi-asserted-by":"publisher","first-page":"1906","DOI":"10.1056\/NEJMoa1915254","article-title":"Randomized trial of Lactin-V to prevent recurrence of bacterial vaginosis","volume":"382","author":"Cohen","year":"2020","journal-title":"N Engl J Med"},{"key":"2026051410074709300_bib8","doi-asserted-by":"publisher","first-page":"102952","DOI":"10.1016\/j.anaerobe.2025.102952","article-title":"Development of a polymicrobial host-bacterial interface biofilm model for bacterial vaginosis","volume":"93","author":"Johnston","year":"2025","journal-title":"Anaerobe"},{"key":"2026051410074709300_bib9","doi-asserted-by":"publisher","first-page":"100101","DOI":"10.1016\/j.bioflm.2022.100101","article-title":"In vitro bacterial vaginosis biofilm community manipulation using endolysin therapy","volume":"5","author":"Johnston","year":"2023","journal-title":"Biofilm"},{"key":"2026051410074709300_bib10","doi-asserted-by":"publisher","first-page":"864","DOI":"10.1097\/OLQ.0b013e318074e565","article-title":"The prevalence of bacterial vaginosis in the United States, 2001\u20132004; associations with symptoms, sexual behaviors, and reproductive health","volume":"34","author":"Koumans","year":"2007","journal-title":"Sex Transm Dis"},{"key":"2026051410074709300_bib11","doi-asserted-by":"publisher","first-page":"1621","DOI":"10.4161\/cc.6.13.4373","article-title":"A novel cell cycle inhibitor stalls replication forks and activates S phase checkpoint","volume":"6","author":"Krishnan","year":"2007","journal-title":"Cell Cycle"},{"key":"2026051410074709300_bib12","doi-asserted-by":"publisher","first-page":"54","DOI":"10.3390\/pathogens10010054","article-title":"Engineered phage endolysin eliminates Gardnerella biofilm without damaging beneficial bacteria in bacterial vaginosis ex vivo","volume":"10","author":"Landlinger","year":"2021","journal-title":"Pathogens"},{"key":"2026051410074709300_bib13","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1016\/j.bpobgyn.2006.12.005","article-title":"Asymptomatic bacterial vaginosis and intermediate flora as risk factors for adverse pregnancy outcome","volume":"21","author":"Leitich","year":"2007","journal-title":"Best Pract Res Clin Obstet Gynaecol"},{"key":"2026051410074709300_bib14","doi-asserted-by":"publisher","first-page":"1856","DOI":"10.1093\/infdis\/jiv338","article-title":"Influence of biofilm formation by Gardnerella vaginalis and other anaerobes on bacterial vaginosis","volume":"212","author":"Machado","year":"2015","journal-title":"J Infect Dis"},{"key":"2026051410074709300_bib15","doi-asserted-by":"publisher","first-page":"1528","DOI":"10.3389\/fmicb.2015.01528","article-title":"Bacterial vaginosis biofilms: challenges to current therapies and emerging solutions","volume":"6","author":"Machado","year":"2016","journal-title":"Front Microbiol"},{"key":"2026051410074709300_bib16","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1089\/aid.2018.0304","article-title":"The evolving facets of bacterial vaginosis: implications for HIV transmission","volume":"35","author":"McKinnon","year":"2019","journal-title":"AIDS Res Hum Retrovir"},{"key":"2026051410074709300_bib17","doi-asserted-by":"publisher","first-page":"726","DOI":"10.1038\/s41570-021-00313-1","article-title":"Towards the sustainable discovery and development of new antibiotics","volume":"5","author":"Miethke","year":"2021","journal-title":"Nat Rev Chem"},{"key":"2026051410074709300_bib18","first-page":"732","article-title":"The estimation of the bactericidal power of the blood","volume":"38","author":"Miles","year":"1938","journal-title":"J Hyg (Lond)"},{"key":"2026051410074709300_bib19","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1097\/QCO.0000000000000620","article-title":"Host-vaginal microbiota interactions in the pathogenesis of bacterial vaginosis","volume":"33","author":"Muzny","year":"2020","journal-title":"Curr Opin Infect Dis"},{"key":"2026051410074709300_bib20","doi-asserted-by":"publisher","first-page":"753","DOI":"10.1021\/jm5012947","article-title":"Structure guided lead generation for M. tuberculosis thymidylate kinase (Mtb TMK): discovery of 3-cyanopyridone and 1,6-naphthyridin-2-one as potent inhibitors","volume":"58","author":"Naik","year":"2015","journal-title":"J Med Chem"},{"key":"2026051410074709300_bib21","doi-asserted-by":"publisher","first-page":"304","DOI":"10.1097\/OLQ.0000000000000972","article-title":"High global burden and costs of bacterial vaginosis: a systematic review and meta-analysis","volume":"46","author":"Peebles","year":"2019","journal-title":"Sexual Trans Dis"},{"key":"2026051410074709300_bib22","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1038\/nrd.2018.168","article-title":"Drug repurposing: progress, challenges and recommendations","volume":"18","author":"Pushpakom","year":"2019","journal-title":"Nat Rev Drug Discov"},{"key":"2026051410074709300_bib23","doi-asserted-by":"publisher","first-page":"513","DOI":"10.18502\/ijm.v15i4.13505","article-title":"Prevalence of Gardnerella vaginalis infection and antibiotic resistance pattern of isolates of gynecology clinic patients at Shahriar Noor Hospital from January to June 2020 by PCR and culture methods","volume":"15","author":"Rashidifar","year":"2023","journal-title":"Iran J Microbiol"},{"key":"2026051410074709300_bib24","doi-asserted-by":"publisher","first-page":"4680","DOI":"10.1073\/pnas.1002611107","article-title":"Vaginal microbiome of reproductive-age women","volume":"108","author":"Ravel","year":"2011","journal-title":"Proc Natl Acad Sci USA"},{"key":"2026051410074709300_bib25","doi-asserted-by":"publisher","first-page":"e9917","DOI":"10.7717\/peerj.9917","article-title":"Evaluation of different culture media to support in vitro growth and biofilm formation of bacterial vaginosis-associated anaerobes","volume":"8","author":"Rosca","year":"2020","journal-title":"PeerJ"},{"key":"2026051410074709300_bib26","doi-asserted-by":"publisher","first-page":"824860","DOI":"10.3389\/fcimb.2022.824860","article-title":"Six bacterial vaginosis-associated species can form an in vitro and ex vivo polymicrobial biofilm that is susceptible to Thymbra capitata essential oil","volume":"12","author":"Rosca","year":"2022","journal-title":"Front Cell Infect Microbiol"},{"key":"2026051410074709300_bib27","doi-asserted-by":"publisher","first-page":"2183","DOI":"10.1093\/jac\/dkac155","article-title":"In vitro interactions within a biofilm containing three species found in bacterial vaginosis (BV) support the higher antimicrobial tolerance associated with BV recurrence","volume":"77","author":"Rosca","year":"2022","journal-title":"J Antimicrob Chemother"},{"key":"2026051410074709300_bib28","doi-asserted-by":"publisher","first-page":"1972","DOI":"10.1093\/jac\/dkaf157","article-title":"Repurposing antimalarials: pyrimethamine exhibits superior in vitro activity to metronidazole against Gardnerella while sparing Lactobacillus","volume":"80","author":"Rosca","year":"2025","journal-title":"J Antimicrob Chemother"},{"key":"2026051410074709300_bib29","doi-asserted-by":"publisher","first-page":"713","DOI":"10.1021\/acsinfecdis.1c00527","article-title":"The Pandemic Response Box\u2014accelerating drug discovery efforts after disease outbreaks","volume":"8","author":"Samby","year":"2022","journal-title":"ACS Infect Dis"},{"key":"2026051410074709300_bib30","doi-asserted-by":"publisher","first-page":"3793","DOI":"10.1007\/s00203-021-02414-3","article-title":"Vaginal microbiome: normalcy vs dysbiosis","volume":"203","author":"Saraf","year":"2021","journal-title":"Arch Microbiol"},{"key":"2026051410074709300_bib31","doi-asserted-by":"publisher","first-page":"737","DOI":"10.1016\/0002-9378(91)90320-Q","article-title":"A new proline aminopeptidase assay for diagnosis of bacterial vaginosis","volume":"165","author":"Schoonmaker","year":"1991","journal-title":"Am J Obstet Gynecol"},{"key":"2026051410074709300_bib32","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.diagmicrobio.2015.10.006","article-title":"Identification of intrinsically metronidazole-resistant clades of Gardnerella vaginalis","volume":"84","author":"Schuyler","year":"2016","journal-title":"Diagn Microbiol Infect Dis"},{"key":"2026051410074709300_bib33","doi-asserted-by":"publisher","first-page":"101444","DOI":"10.1016\/j.nmni.2024.101444","article-title":"Evaluation of MMV Pandemic Response Box compounds to identify potent compounds against clinically relevant bacterial and fungal clinical isolates in vitro","volume":"60","author":"Sivasankar","year":"2024","journal-title":"New Microbes New Infect"},{"key":"2026051410074709300_bib34","doi-asserted-by":"publisher","first-page":"1586","DOI":"10.1128\/AAC.00940-08","article-title":"In vitro activities of retigeric acid B alone and in combination with azole antifungal agents against Candida albicans","volume":"53","author":"Sun","year":"2009","journal-title":"Antimicrob Agents Chemother"},{"key":"2026051410074709300_bib35","doi-asserted-by":"publisher","first-page":"284762","DOI":"10.1155\/2012\/284762","article-title":"Susceptibility of Gardnerella vaginalis biofilms to natural antimicrobials subtilosin, \u03b5-poly-L-lysine, and lauramide arginine ethyl ester","volume":"2012","author":"Turovskiy","year":"2012","journal-title":"Infect Dis Obstet Gynecol"},{"key":"2026051410074709300_bib36","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1186\/s12916-021-02077-3","article-title":"Bacterial vaginosis: drivers of recurrence and challenges and opportunities in partner treatment","volume":"19","author":"Vodstrcil","year":"2021","journal-title":"BMC Med"},{"key":"2026051410074709300_bib37","doi-asserted-by":"publisher","first-page":"e00924","DOI":"10.1128\/AAC.00924-20","article-title":"Screening repurposing libraries for identification of drugs with novel antifungal activity","volume":"64","author":"Wall","year":"2020","journal-title":"Antimicrob Agents Chemother"},{"key":"2026051410074709300_bib38","doi-asserted-by":"publisher","first-page":"5150","DOI":"10.1016\/j.bmcl.2005.08.055","article-title":"Phosphinate, sulfonate, and sulfonamidate dipeptides as potential inhibitors of Escherichia coli aminopeptidase N","volume":"15","author":"Yang","year":"2005","journal-title":"Bioorg Med Chem Lett"},{"key":"2026051410074709300_bib39","doi-asserted-by":"publisher","first-page":"1009798","DOI":"10.3389\/fmicb.2022.1009798","article-title":"Antibiotic resistance and pathogenicity assessment of various Gardnerella sp. strains in local China","volume":"13","author":"Zhang","year":"2022","journal-title":"Front Microbiol"},{"key":"2026051410074709300_bib40","doi-asserted-by":"publisher","first-page":"587","DOI":"10.1016\/j.gpb.2022.01.004","article-title":"SynergyFinder Plus: toward better interpretation and annotation of drug combination screening datasets","volume":"20","author":"Zheng","year":"2022","journal-title":"Genom Proteom Bioinform"}],"container-title":["Journal of Applied Microbiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jambio\/advance-article-pdf\/doi\/10.1093\/jambio\/lxag034\/66631315\/lxag034.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jambio\/article-pdf\/137\/2\/lxag034\/66631315\/lxag034.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jambio\/article-pdf\/137\/2\/lxag034\/66631315\/lxag034.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T14:07:54Z","timestamp":1778767674000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jambio\/article\/doi\/10.1093\/jambio\/lxag034\/8444583"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,29]]},"references-count":40,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2026,2,2]]}},"URL":"https:\/\/doi.org\/10.1093\/jambio\/lxag034","relation":{},"ISSN":["1365-2672"],"issn-type":[{"value":"1365-2672","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,2]]},"published":{"date-parts":[[2026,1,29]]},"article-number":"lxag034"}}