{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T16:44:12Z","timestamp":1789922652682,"version":"4.0.1"},"reference-count":25,"publisher":"American Society for Microbiology","issue":"8","license":[{"start":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T00:00:00Z","timestamp":1785888000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T00:00:00Z","timestamp":1785888000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"Innovative Medicines Initiatives 2 Joint Undertaking","award":["No 853989"],"award-info":[{"award-number":["No 853989"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2026,8,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      GSK2556286 (GSK286) is a novel drug candidate with a cholesterol-dependent mode of action that has shown promising\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      potential to improve tuberculosis treatment when combined with bedaquiline (B) and pretomanid (Pa). This study explored the\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      activity of GSK286 alone and in combination with B and Pa, using extracellular and intracellular dose-response time-kill assays against different\n                      <jats:italic toggle=\"yes\">Mycobacterium tuberculosis<\/jats:italic>\n                      (Mtb) strains. GSK286 demonstrated media-specific activity, inhibiting Mtb growth only in cholesterol- and propionate-containing media, with slight activity against both extracellular and intracellular Mtb. The Mtb strain overexpressing Mtb adenylyl cyclase\n                      <jats:italic toggle=\"yes\">Rv1625c<\/jats:italic>\n                      exhibited higher susceptibility to GSK286, whereas the\n                      <jats:italic toggle=\"yes\">Rv1625c<\/jats:italic>\n                      mutant was more resistant. This confirms GSK286\u2019s mechanism of action linked to\n                      <jats:italic toggle=\"yes\">Rv1625c<\/jats:italic>\n                      . GSK286 combined with BPa was bactericidal, although the main driver of this interaction was observed between GSK286 and B, with potency comparable to that of the triple BPa + GSK286 regimen, both extracellularly and intracellularly. These findings suggest that GSK286 may be a promising companion to B, with or without Pa, particularly under conditions with a sub-optimal B dose, where the GSK286 + B interaction was more clearly observed. These studies offer new insights into this drug combination to guide future research toward better tuberculosis treatments.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/aac.00260-26","type":"journal-article","created":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T13:58:57Z","timestamp":1783951137000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":1,"title":["<i>In vitro<\/i>\n                    characterization of GSK2556286 in combination with bedaquiline and pretomanid against\n                    <i>Mycobacterium tuberculosis<\/i>"],"prefix":"10.1128","volume":"70","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4630-5446","authenticated-orcid":true,"given":"Marie Sylvianne","family":"Rabodoarivelo","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/012a91z28","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology, Pediatrics, Radiology and Public Health, Faculty of Medicine, University of Zaragoza","place":["Zaragoza, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5029-325X","authenticated-orcid":false,"given":"Jordana","family":"Galizia","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/012a91z28","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology, Pediatrics, Radiology and Public Health, Faculty of Medicine, University of Zaragoza","place":["Zaragoza, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah","family":"Recchia","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00s6t1f81","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biology and Biotechnology Lazzaro Spallanzani, University of Pavia","place":["Pavia, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Stamilla","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00s6t1f81","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biology and Biotechnology Lazzaro Spallanzani, University of Pavia","place":["Pavia, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1587-6692","authenticated-orcid":true,"given":"Michael","family":"Dal Molin","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00rcxh774","id-type":"ROR","asserted-by":"publisher"}],"name":"Division of Infectious Diseases, Department I of Internal Medicine, University of Cologne","place":["Cologne, Germany"]},{"id":[{"id":"https:\/\/ror.org\/00rcxh774","id-type":"ROR","asserted-by":"publisher"}],"name":"Faculty of Medicine, Center for Molecular Medicine Cologne (CMMC), University of Cologne","place":["Cologne, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4224-1091","authenticated-orcid":false,"given":"Eik","family":"Hoffmann","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05k9skc85","id-type":"ROR","asserted-by":"publisher"}],"name":"University of Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019-UMR 8204, Centre d'Infection et d'Immunit\u00e9 de Lille (CIIL)","place":["Lille, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cyril","family":"Gaudin","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05k9skc85","id-type":"ROR","asserted-by":"publisher"}],"name":"University of Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019-UMR 8204, Centre d'Infection et d'Immunit\u00e9 de Lille (CIIL)","place":["Lille, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1542-9163","authenticated-orcid":false,"given":"Maxime","family":"Eveque","sequence":"additional","affiliation":[{"name":"University of Lille, Inserm, Institut Pasteur de Lille, U1177-Drugs and Molecules for Living Systems","place":["Lille, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominique","family":"Ndjogou","sequence":"additional","affiliation":[{"name":"University of Lille, Inserm, Institut Pasteur de Lille, U1177-Drugs and Molecules for Living Systems","place":["Lille, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebeca","family":"Bailo","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/012a91z28","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology, Pediatrics, Radiology and Public Health, Faculty of Medicine, University of Zaragoza","place":["Zaragoza, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albin A. 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