{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T00:42:06Z","timestamp":1792024926437,"version":"4.4.0"},"reference-count":38,"publisher":"American Society for Microbiology","issue":"10","license":[{"start":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T00:00:00Z","timestamp":1761177600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T00:00:00Z","timestamp":1761177600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["GM121650"],"award-info":[{"award-number":["GM121650"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI158706"],"award-info":[{"award-number":["AI158706"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Bacteriol"],"published-print":{"date-parts":[[2025,10,23]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      New antibiotics with novel mechanisms of action are needed to treat infections by multidrug-resistant strains of\n                      <jats:italic toggle=\"yes\">Mycobacterium tuberculosis<\/jats:italic>\n                      . Here, we show that KKL-1005, an anti-tubercular triazole-based molecule, binds to ribosomal protein bL12 and specifically inhibits the\n                      <jats:italic toggle=\"yes\">trans<\/jats:italic>\n                      -translation ribosome rescue pathway, a process essential for the survival of\n                      <jats:italic toggle=\"yes\">M. tuberculosis<\/jats:italic>\n                      . Our data demonstrate that KKL-1005 binds to the N-terminal domain of bL12, both\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      and in bacterial cells, and specifically inhibits\n                      <jats:italic toggle=\"yes\">trans<\/jats:italic>\n                      -translation and not normal translation. These results suggest that tmRNA-SmpB interacts with bL12 differently from tRNA and raise the possibility of developing antibiotics targeting bL12.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        Tuberculosis continues to be a leading cause of death worldwide, and antibiotics that target new pathways are urgently needed.\n                        <jats:italic toggle=\"yes\">trans<\/jats:italic>\n                        -Translation is a ribosome rescue pathway required for the survival of\n                        <jats:italic toggle=\"yes\">Mycobacterium tuberculosis<\/jats:italic>\n                        . We identified a small molecule, KKL-1005, that specifically inhibits\n                        <jats:italic toggle=\"yes\">trans<\/jats:italic>\n                        -translation without affecting translation from a library of compounds that prevent the growth of\n                        <jats:italic toggle=\"yes\">M. tuberculosis<\/jats:italic>\n                        . KKL-1005 targets bacterial ribosomal protein bL12, which is essential for the recruitment and activation of GTPase translation factors. The specificity of KKL-1005 for\n                        <jats:italic toggle=\"yes\">trans<\/jats:italic>\n                        -translation indicates that bL12 interacts differently with the translation machinery during\n                        <jats:italic toggle=\"yes\">trans<\/jats:italic>\n                        -translation than during canonical translation. KKL-1005 is bactericidal against\n                        <jats:italic toggle=\"yes\">M. tuberculosis<\/jats:italic>\n                        , suggesting that inhibiting\n                        <jats:italic toggle=\"yes\">trans<\/jats:italic>\n                        -translation by targeting bL12 is a new strategy for developing antibiotics against drug-resistant infections.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/jb.00236-25","type":"journal-article","created":{"date-parts":[[2025,9,3]],"date-time":"2025-09-03T13:01:36Z","timestamp":1756904496000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":5,"title":["A\n                    <i>trans<\/i>\n                    -translation inhibitor that targets ribosomal protein bL12 kills\n                    <i>Mycobacterium tuberculosis<\/i>"],"prefix":"10.1128","volume":"207","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-4524-3523","authenticated-orcid":false,"given":"Akanksha","family":"Varshney","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00hj54h04","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Molecular Biosciences, The University of Texas at Austin","place":["Austin, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John N.","family":"Alumasa","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Pennsylvania State University","place":["University Park, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amber","family":"Miller","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Pennsylvania State University","place":["University Park, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8753-335X","authenticated-orcid":true,"given":"Kenneth C.","family":"Keiler","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00hj54h04","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Molecular Biosciences, The University of Texas at Austin","place":["Austin, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","unstructured":"World Health Organization. 2024. Global tuberculosis report. https:\/\/www.who.int\/teams\/global-programme-on-tuberculosis-and-lung-health\/tb-reports\/global-tuberculosis-report-2024."},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2022.954074"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-025-89087-w"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1021\/acsinfecdis.7b00028"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tube.2013.09.007"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro3438"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.271.5251.990"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0028413"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/18.13.3793"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi992439d"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aav9370"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature11006"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.191375298"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.12.9.1338"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.12.9.1348"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1302816110"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1021\/acsinfecdis.4c00963"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2015.00498"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.3418"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M313384200"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/0300-9084(87)90004-6"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi0495331"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2005.04.015"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/19.2.174"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1802001115"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2006.10.025"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2010.04.009"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.275.2.890"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.2174\/1389203023380756"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biochi.2020.06.006"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2003.12.080"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7600884"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1128\/mbio.01461-23"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1261\/rna.045773.114"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1261\/rna.042226.113"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-24881-4"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1086\/510431"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1021\/acssynbio.8b00427"}],"container-title":["Journal of Bacteriology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/jb.00236-25","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/jb.00236-25","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T13:21:13Z","timestamp":1761225673000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/jb.00236-25"}},"subtitle":[],"editor":[{"given":"Patricia A.","family":"Champion","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,10,23]]},"references-count":38,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2025,10,23]]}},"alternative-id":["10.1128\/jb.00236-25"],"URL":"https:\/\/doi.org\/10.1128\/jb.00236-25","relation":{},"ISSN":["0021-9193","1098-5530"],"issn-type":[{"value":"0021-9193","type":"print"},{"value":"1098-5530","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,23]]},"assertion":[{"value":"2025-06-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-05","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-03","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e00236-25"}}