{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T15:46:00Z","timestamp":1787240760884,"version":"build-2736575974"},"reference-count":46,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2025,5,7]],"date-time":"2025-05-07T00:00:00Z","timestamp":1746576000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,5,7]],"date-time":"2025-05-07T00:00:00Z","timestamp":1746576000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["1R01AI179827"],"award-info":[{"award-number":["1R01AI179827"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2025,5,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Aligned with the World Health Organization\u2019s Road Map, there is an unmet need for research to improve the treatment of Buruli ulcer caused by\n                      <jats:italic toggle=\"yes\">Mycobacterium ulcerans<\/jats:italic>\n                      . The repurposing of drugs could speed up new regimen development to treat Buruli ulcer. Using a virulent reporter strain of\n                      <jats:italic toggle=\"yes\">M. ulcerans<\/jats:italic>\n                      with intrinsic bioluminescence (MuAL), we compared the minimum inhibitory concentration (MIC) of moxifloxacin, bedaquiline, telacebec, tebipenem, omadacycline, and epetraborole with standard-of-care drugs\u2014rifampin and clarithromycin. We also compared the efficacy (maximal kill or\n                      <jats:italic toggle=\"yes\">E<\/jats:italic>\n                      <jats:sub>max<\/jats:sub>\n                      ) and potency (EC\n                      <jats:sub>50<\/jats:sub>\n                      or concentration associated with 50% of\n                      <jats:italic toggle=\"yes\">E<\/jats:italic>\n                      <jats:sub>max<\/jats:sub>\n                      ) as single and two-drug combinations. The doubling time of MuAL was calculated as 3.66 (95% CI: 3.41\u20133.93) days. Telacebec had the lowest MIC (0.0000075 mg\/L) among the eight drugs tested, followed by rifampicin (0.5 mg\/L) and clarithromycin (0.5 mg\/L). Epetraborole, telacebec, and moxifloxacin monotherapy at tested concentrations showed higher\n                      <jats:italic toggle=\"yes\">E<\/jats:italic>\n                      <jats:sub>max<\/jats:sub>\n                      compared to clarithromycin and rifampicin. In preclinical studies, telacebec combined with rifampicin or epetraborole and epetraborole combinations with moxifloxacin and omadacycline were superior to the rifampin-clarithromycin combination. The MuAL strain is useful in the rapid screening of drugs\u2019 efficacy and potency against\n                      <jats:italic toggle=\"yes\">M. ulcerans<\/jats:italic>\n                      . We should leverage the progress made in the tuberculosis drug development pipeline to repurpose the drugs for the rapid development of new therapeutic modalities for Buruli ulcer.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/aac.00029-25","type":"journal-article","created":{"date-parts":[[2025,3,26]],"date-time":"2025-03-26T10:38:24Z","timestamp":1742985504000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":5,"title":["Repurposing drugs to advance the treatment of Buruli ulcer"],"prefix":"10.1128","volume":"69","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4601-5673","authenticated-orcid":true,"given":"Sanjay","family":"Singh","sequence":"first","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, School of Medicine, University of Texas Health Science Centre at Tyler","place":["Tyler, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rie","family":"Yotsu","sequence":"additional","affiliation":[{"name":"Department of Tropical Medicine and Infectious Disease, School of Public Health and Tropical Medicine, Tulane University","place":["New Orleans, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1440-9889","authenticated-orcid":true,"given":"Eric","family":"Nuremberger","sequence":"additional","affiliation":[{"name":"Center for Tuberculosis Research, Division of Infectious Diseases, Johns Hopkins University School of Medicine","place":["Baltimore, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8786-8851","authenticated-orcid":true,"given":"Shashikant","family":"Srivastava","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, School of Medicine, University of Texas Health Science Centre at Tyler","place":["Tyler, USA"]},{"name":"Department of Cellular and Molecular Biology, Center for Biomedical Research, University of Texas Health Science Centre at Tyler","place":["Tyler, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","unstructured":"WHO. 2023. Buruli ulcer (Mycobacterium ulcerans infection). Available from: https:\/\/www.who.int\/en\/news-room\/fact-sheets\/detail\/buruli-ulcer-(mycobacterium-ulcerans-infection). Retrieved 8 Jan 2023."},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2214-109X(19)30171-8"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid2512.190427"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijid.2018.10.012"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1111\/1346-8138.17483"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1111\/cmi.12547"},{"key":"e_1_3_3_8_2","volume-title":"Treatment of Mycobacterium ulcerans disease (Buruli ulcer). Guidance for health workers","author":"WHO","year":"2012","unstructured":"WHO. 2012. Treatment of Mycobacterium ulcerans disease (Buruli ulcer). Guidance for health workers. World Health Organization Team, Switzerland."},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.31128\/AJGP-08-23-6914"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD012118.pub2"},{"key":"e_1_3_3_11_2","unstructured":"Clinicaltials.gov. 2021. Beta-lactam containing regimen for the shortening of Buruli ulcer disease therapy (BLMs4BU). NCT05169554. www.clinicaltrials.gov. Available from: https:\/\/classic.clinicaltrials.gov\/ct2\/show\/NCT05169554?cond=Buruli+Ulcer&draw=1&rank=1"},{"key":"e_1_3_3_12_2","volume-title":"Ending the neglect to attain the sustainable development goals. A road map for neglected tropical diseases 2021\u20132030","author":"WHO","year":"2020","unstructured":"WHO. 2020. Ending the neglect to attain the sustainable development goals. A road map for neglected tropical diseases 2021\u20132030. World Health Organization, Switzerland."},{"key":"e_1_3_3_13_2","unstructured":"No Author Listed. 2024. NCATS drug repurposing. Seeking new treatments using existing drugs. Sciences NCfAT NCATS\/NIH. Available from: www.ncats.nih.gov\/preclinical\/repurpose. https:\/\/ncats.nih.gov\/sites\/default\/files\/2023-11\/NCATS-2023_Drug-Repurposing-Fact-Sheet-508.pdf"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00400-10"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01260-10"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0002598"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-024-02840-y"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/aac.00687-22"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/aac.01080-23"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2023.106847"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00990-16"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01761-09"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciw474"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02821-15"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciy627"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.04441-14"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1093\/ofid\/ofac492.1334"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01156-21"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1009965"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00259-20"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3262"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc1412235"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2020.11.007"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0924-8579(03)00240-1"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0009-9236(03)00201-7"},{"key":"e_1_3_3_36_2","first-page":"89","volume-title":"Drug susceptibility in chemotherapy of mycobacterial infections","author":"Peloquin CA","year":"1991","unstructured":"Peloquin CA. 1991. 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