{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T10:17:28Z","timestamp":1785406648891,"version":"3.56.0"},"reference-count":65,"publisher":"American Society for Microbiology","issue":"8","license":[{"start":{"date-parts":[[2025,8,13]],"date-time":"2025-08-13T00:00:00Z","timestamp":1755043200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,8,13]],"date-time":"2025-08-13T00:00:00Z","timestamp":1755043200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI026170"],"award-info":[{"award-number":["AI026170"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2025,8,13]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Tuberculosis (TB), a disease caused by the bacterium\n                      <jats:italic toggle=\"yes\">Mycobacterium tuberculosis<\/jats:italic>\n                      (\n                      <jats:italic toggle=\"yes\">Mtb<\/jats:italic>\n                      ), continues to pose a major global health threat, exacerbated by the emergence of drug-resistant strains and the lengthy treatment regimens required for effective management. Bedaquiline (BDQ), a key component in novel regimens for multidrug-resistant (MDR) TB, has demonstrated significant efficacy but is threatened by rising resistance. Our study investigates the potential of vitamin C to enhance BDQ\u2019s activity and prevent resistance. We found that combining BDQ with vitamin C sterilized drug-susceptible and MDR\n                      <jats:italic toggle=\"yes\">Mtb<\/jats:italic>\n                      cultures\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      within 21 days, achieving a 6-log reduction in colony-forming units. This combination also enhanced\n                      <jats:italic toggle=\"yes\">Mtb<\/jats:italic>\n                      killing in infected human macrophages and peripheral blood mononuclear cells. Transcriptomic analysis revealed that the BDQ\/vitamin C combination induces widespread metabolic disruption in\n                      <jats:italic toggle=\"yes\">Mtb<\/jats:italic>\n                      , characterized by upregulation of stress response and metal ion homeostasis genes and downregulation of energy metabolism and cell wall biosynthesis genes. Mechanistic studies implicated reactive oxygen species and disrupted copper homeostasis as contributing factors to the sterilization effect. These findings highlight the potential of using vitamin C as an adjunct therapy with BDQ, offering a promising strategy to enhance drug efficacy and mitigate emerging drug resistance during MDR-TB treatment.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>IMPORTANCE<\/jats:title>\n                    <jats:p>\n                      Tuberculosis (TB) remains a major global health problem, especially as drug-resistant forms become more common and harder to treat. Bedaquiline is one of the most important new drugs for treating these resistant infections, but resistance to bedaquiline is also starting to appear. This study found that the combination of vitamin C and bedaquiline sterilizes\n                      <jats:italic toggle=\"yes\">Mycobacterium tuberculosis<\/jats:italic>\n                      cultures\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      while potentiating bedaquiline activity in infected human macrophage cells. The combination appears to overwhelm the bacteria by creating stress and disrupting essential functions, like energy production and metal balance. These results suggest that vitamin C, a safe and inexpensive supplement, could be used alongside existing drugs to make treatment faster and more effective while also helping to prevent resistance.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/mbio.01484-25","type":"journal-article","created":{"date-parts":[[2025,6,25]],"date-time":"2025-06-25T09:00:31Z","timestamp":1750842031000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":10,"title":["Vitamin C potentiates the killing of\n                    <i>Mycobacterium tuberculosis<\/i>\n                    by bedaquiline through metabolic disruption"],"prefix":"10.1128","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5960-6670","authenticated-orcid":false,"given":"Catherine","family":"Vilch\u00e8ze","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05cf8a891","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology and Immunology, Albert Einstein College of Medicine","place":["Bronx, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saranathan","family":"Rajagopalan","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05cf8a891","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology and Immunology, Albert Einstein College of Medicine","place":["Bronx, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raja Sab","family":"Kalluru","sequence":"additional","affiliation":[{"name":"Department of Pathology, Stanford University School of Medicine","place":["Stanford, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niaz","family":"Banaei","sequence":"additional","affiliation":[{"name":"Department of Pathology, Stanford University School of Medicine","place":["Stanford, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3321-3080","authenticated-orcid":true,"suffix":"Jr.","given":"William R.","family":"Jacobs","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05cf8a891","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology and Immunology, Albert Einstein College of Medicine","place":["Bronx, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_5_2_2","unstructured":"World Health Organization. 2023. Global tuberculosis report 2023. Available from: https:\/\/cdn.who.int\/media\/docs\/default-source\/hq-tuberculosis\/global-tuberculosis-report-2023\/global-tb-report-2023-factsheet.pdf?sfvrsn=f0dfc8a4_4&download=true"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1186\/s40545-023-00577-6"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.mjt.0000433951.09030.5a"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijtb.2016.01.031"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0002-9343(96)00402-0"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1378\/chest.76.6_supplement.741"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2117166"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13063-023-07701-6"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciad312"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2119430"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1901814"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-2600(23)00389-2"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jobb.2024.01.001"},{"key":"e_1_3_5_15_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid3003.240134"},{"key":"e_1_3_5_16_2","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.00621-2021"},{"key":"e_1_3_5_17_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1106753"},{"key":"e_1_3_5_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio884"},{"key":"e_1_3_5_19_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkaa136"},{"key":"e_1_3_5_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2666-5247(23)00172-6"},{"key":"e_1_3_5_21_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc2103049"},{"key":"e_1_3_5_22_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkx094"},{"key":"e_1_3_5_23_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2021.754249"},{"key":"e_1_3_5_24_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkv150"},{"key":"e_1_3_5_25_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00753-16"},{"key":"e_1_3_5_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jgar.2023.04.003"},{"key":"e_1_3_5_27_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkw502"},{"key":"e_1_3_5_28_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1704376114"},{"key":"e_1_3_5_29_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02165-17"},{"key":"e_1_3_5_30_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01703-20"},{"key":"e_1_3_5_31_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0007778"},{"key":"e_1_3_5_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms2898"},{"key":"e_1_3_5_33_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1523321113"},{"key":"e_1_3_5_34_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3001906"},{"key":"e_1_3_5_35_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-4658.2009.07066.x"},{"key":"e_1_3_5_36_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M117.797837"},{"key":"e_1_3_5_37_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-86477-8"},{"key":"e_1_3_5_38_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.01092-17"},{"key":"e_1_3_5_39_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.2001.02684.x"},{"key":"e_1_3_5_40_2","doi-asserted-by":"publisher","DOI":"10.1128\/spectrum.03604-22"},{"key":"e_1_3_5_41_2","doi-asserted-by":"publisher","DOI":"10.1186\/1472-6904-2-8"},{"key":"e_1_3_5_42_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23105713"},{"key":"e_1_3_5_43_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1009261108"},{"key":"e_1_3_5_44_2","doi-asserted-by":"publisher","DOI":"10.1039\/c4mt00305e"},{"key":"e_1_3_5_45_2","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio844"},{"key":"e_1_3_5_46_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.01847-07"},{"key":"e_1_3_5_47_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R115.640193"},{"key":"e_1_3_5_48_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0169545"},{"key":"e_1_3_5_49_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0900589106"},{"key":"e_1_3_5_50_2","doi-asserted-by":"publisher","DOI":"10.1128\/msphere.00573-22"},{"key":"e_1_3_5_51_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.187.17.6137-6146.2005"},{"key":"e_1_3_5_52_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2011.00105"},{"key":"e_1_3_5_53_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2006.05028.x"},{"key":"e_1_3_5_54_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms4369"},{"key":"e_1_3_5_55_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-19959-4"},{"key":"e_1_3_5_56_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22062938"},{"key":"e_1_3_5_57_2","doi-asserted-by":"publisher","DOI":"10.3945\/an.110.000109"},{"key":"e_1_3_5_58_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-140-7-200404060-00010"},{"key":"e_1_3_5_59_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.8.3704"},{"key":"e_1_3_5_60_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.171318198"},{"key":"e_1_3_5_61_2","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1983.54.1.208"},{"key":"e_1_3_5_62_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00938-18"},{"key":"e_1_3_5_63_2","doi-asserted-by":"publisher","DOI":"10.1006\/mben.2001.0220"},{"key":"e_1_3_5_64_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.178.20.6013-6018.1996"},{"key":"e_1_3_5_65_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ab.2004.03.049"},{"key":"e_1_3_5_66_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.01245-14"}],"container-title":["mBio"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/mbio.01484-25","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/mbio.01484-25","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,13]],"date-time":"2025-08-13T13:04:11Z","timestamp":1755090251000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/mbio.01484-25"}},"subtitle":[],"editor":[{"given":"K. Heran","family":"Darwin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,8,13]]},"references-count":65,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2025,8,13]]}},"alternative-id":["10.1128\/mbio.01484-25"],"URL":"https:\/\/doi.org\/10.1128\/mbio.01484-25","relation":{},"ISSN":["2150-7511"],"issn-type":[{"value":"2150-7511","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,13]]},"assertion":[{"value":"2025-05-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-05-27","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-06-25","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e01484-25"}}