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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2026,1,20]]},"abstract":"<jats:p>\n                    Unlike commonly studied rod-shaped bacteria, mycobacteria grow from their poles, requiring precise coordination between division and initiation of new pole growth. The mechanisms that mediate this transition are largely unknown, but likely represent a rich source of drug targets for the treatment of mycobacterial infections, including tuberculosis. Here, we identify TapA (MSMEG_3748\/Rv1697) as a key regulator of this transition. TapA interacts with the sensor kinase MtrB at the septum to initiate a signaling cascade that ultimately results in the expression of the essential peptidoglycan hydrolases RipAB, among others, at the end of division. Loss of TapA disrupts division, dysregulates pole formation, and sensitizes\n                    <jats:italic toggle=\"yes\">\n                      <jats:italic toggle=\"yes\">Mycobacterium tuberculosis<\/jats:italic>\n                    <\/jats:italic>\n                    and other mycobacteria to several first and second-line TB antibiotics, establishing TapA as a potential therapeutic target, and defining a link between cell cycle progression, envelope remodeling, and intrinsic antibiotic resistance in mycobacteria.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2519608123","type":"journal-article","created":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T17:06:13Z","timestamp":1768583173000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":1,"title":["An activator of a two-component system controls cell separation and intrinsic drug resistance in\n                    <i>\n                      <i>Mycobacterium tuberculosis<\/i>\n                    <\/i>"],"prefix":"10.1073","volume":"123","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1251-7678","authenticated-orcid":false,"given":"Liam D.","family":"McDonough","sequence":"first","affiliation":[{"name":"Department of Microbial Pathogenesis, Yale University School of Medicine","place":["New Haven"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuqi","family":"Li","sequence":"additional","affiliation":[{"name":"Laboratory of Host-Pathogen Biology, The Rockefeller University","place":["New York"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-0925-9632","authenticated-orcid":false,"given":"Vanisha","family":"Munsamy-Govender","sequence":"additional","affiliation":[{"name":"Laboratory of Host-Pathogen Biology, The Rockefeller University","place":["New York"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8928-7970","authenticated-orcid":false,"given":"Celena M.","family":"Gwin","sequence":"additional","affiliation":[{"name":"Department of Microbial Pathogenesis, Yale University School of Medicine","place":["New Haven"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9310-951X","authenticated-orcid":false,"given":"Jeremy M.","family":"Rock","sequence":"additional","affiliation":[{"name":"Laboratory of Host-Pathogen Biology, The Rockefeller University","place":["New York"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2973-8354","authenticated-orcid":false,"given":"E. 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Hartmans J. A. M. de Bont E. Stackebrandt \"The genus mycobacterium--nonmedical\" in The Prokaryotes M. Dworkin S. Falkow E. Rosenberg K. H. Schleifer E. Stackebrandt Eds. (Springer 2006) pp. 889\u2013918.","DOI":"10.1007\/0-387-30743-5_33"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2018.09.004"},{"key":"e_1_3_4_15_2","doi-asserted-by":"crossref","unstructured":"G. Carloni Mechanistic insights into the allosteric regulation of cell wall hydrolase RipA in Mycobacterium tuberculosis. bioRxiv [Preprint] (2025). https:\/\/doi.org\/10.1101\/2025.06.28.662095 (Accessed 30 November 2025).","DOI":"10.1101\/2025.06.28.662095"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41564-022-01130-y"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01334-17"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1315-z"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.180.5.1037-1043.1998"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1003197"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00059-16"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.346544"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.69.1.183"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2010.07110.x"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2006.08.005"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.01795-14"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.10.5752"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00616-15"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.185.1.89-97.2003"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1009148"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1002\/pmic.201000472"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.02061-05"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-1097(03)00964-9"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.4074"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2020.07.070"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gni013"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.15252\/embj.201695028"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2011.07601.x"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2019.06.005"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-024-07487-w"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80995-2"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2012.05.036"},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.00384-22"},{"key":"e_1_3_4_44_2","doi-asserted-by":"crossref","unstructured":"M. H. Lee L. Pascopella W. R. Jacobs Jr. G. F. Hatfull Site-specific integration of mycobacteriophage L5: integration-proficient vectors for Mycobacterium smegmatis Mycobacterium tuberculosis and bacille Calmette-Guerin. Proc. Natl. Acad. Sci. U.S.A. 88 3111\u20133115 (1991).","DOI":"10.1073\/pnas.88.8.3111"},{"key":"e_1_3_4_45_2","doi-asserted-by":"publisher","DOI":"10.1099\/mic.0.2007\/008904-0"},{"key":"e_1_3_4_46_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmicrobiol.2016.274"},{"key":"e_1_3_4_47_2","doi-asserted-by":"crossref","unstructured":"B. Bosch . Genome-wide gene expression tuning reveals diverse vulnerabilities of M. tuberculosis. Cell 184 4579\u20134592 e4524 (2021).","DOI":"10.1016\/j.cell.2021.06.033"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2519608123","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T17:07:00Z","timestamp":1768583220000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/10.1073\/pnas.2519608123"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,16]]},"references-count":47,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,1,20]]}},"alternative-id":["10.1073\/pnas.2519608123"],"URL":"https:\/\/doi.org\/10.1073\/pnas.2519608123","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,16]]},"assertion":[{"value":"2025-07-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-18","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-16","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2519608123"}}