{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T07:43:19Z","timestamp":1792827799177,"version":"4.5.0"},"reference-count":52,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2025,5,8]],"date-time":"2025-05-08T00:00:00Z","timestamp":1746662400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100019122","name":"Fondation Raoul Follereau","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100019122","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>New drugs targeting the electron transport chain (ETC) seem to be a promising advance in leprosy treatment. In this study, we evaluated the bactericidal activity of telacebec (TCB), a phase 2 drug candidate for tuberculosis, alongside known ETC-targeting antibiotics, bedaquiline (BDQ) and clofazimine (CFZ), as monotherapy or in combination.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methodology\/ Principal Findings<\/jats:title>\n<jats:p>We used the reference leprosy proportional bactericidal mouse footpad model. Four hundred and ten mice were inoculated in the footpads with 5x10<jats:sup>4<\/jats:sup> to 5x10<jats:sup>0<\/jats:sup> bacilli of <jats:italic>M. leprae<\/jats:italic> strain THAI53 for the untreated control group and groups treated with drug-monotherapies, and with 5x10<jats:sup>4<\/jats:sup> to 5x10<jats:sup>1<\/jats:sup> for groups treated with drug-combinations. Mice were randomly allocated into the following groups: 2 control groups (untreated or standard multi drug therapy (MDT), rifampin, dapsone and clofazimine with dosing equipotent to human dosing) and 7 test groups (TCB 10mg\/kg, bedaquiline 25mg\/kg (BDQ), clofazimine 20mg\/kg (CFZ), CFZ\u2009+\u2009BDQ, TCB\u2009+\u2009BDQ, TCB\u2009+\u2009CFZ, TCB\u2009+\u2009CFZ\u2009+\u2009BDQ). Mice in the test groups received either one month treatment (MDT) or a single dose of the drugs (TCB, RIF, BDQ, CFZ). Twelve months later, mice were sacrificed to enumerate <jats:italic>M. leprae<\/jats:italic> bacilli in the footpad. All the footpads became negative in the MDT, TCB and combination groups except in the TCB\u2009+\u2009CFZ group where 2 mice remained positive in the 5x10<jats:sup>4<\/jats:sup> inoculum.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Conclusion<\/jats:title>\n<jats:p>We demonstrated that monotherapy of TCB exhibited bactericidal activity against <jats:italic>M. leprae<\/jats:italic> comparable to that of MDT and that all combination therapies were as effective as MDT, except the combination TCB\u2009+\u2009CFZ, possibly due to an antagonism between these two drugs.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pntd.0013076","type":"journal-article","created":{"date-parts":[[2025,5,8]],"date-time":"2025-05-08T17:37:37Z","timestamp":1746725857000},"page":"e0013076","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":6,"title":["Unprecedented in vivo activity of telacebec against Mycobacterium 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