{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T01:47:51Z","timestamp":1785548871057,"version":"3.56.0"},"update-to":[{"DOI":"10.1371\/journal.ppat.1014131","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T00:00:00Z","timestamp":1777420800000}}],"reference-count":56,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T00:00:00Z","timestamp":1776816000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"funder":[{"DOI":"10.13039\/100000738","name":"U.S. Department of Veterans Affairs","doi-asserted-by":"publisher","award":["1I01BX004527-01A1"],"award-info":[{"award-number":["1I01BX004527-01A1"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","award":["OPP1170003"],"award-info":[{"award-number":["OPP1170003"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","award":["OPP1170003"],"award-info":[{"award-number":["OPP1170003"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"US National Institutes of Health","doi-asserted-by":"crossref","award":["UM1 AI179699"],"award-info":[{"award-number":["UM1 AI179699"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"US National Institutes of Health","doi-asserted-by":"crossref","award":["UM1 AI179699"],"award-info":[{"award-number":["UM1 AI179699"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    Post-antibiotic effect (PAE) describes the delay in bacterial growth that continues after antibiotics are cleared. The physiologic basis of PAE in Mycobacterium tuberculosis (\n                    <jats:italic>Mtb<\/jats:italic>\n                    ) remains poorly understood. Here, we evaluated the long-standing hypothesis that PAE reflects the time required for bacteria to recover from drug-induced physiologic damage by comparing\n                    <jats:italic>Mtb<\/jats:italic>\n                    after varying durations of treatment with the four-drug isoniazid, rifampin, pyrazinamide, ethambutol combination\n                    <jats:italic>in vitro<\/jats:italic>\n                    and in BALB\/c mice using two novel molecular readouts of bacterial health. In aerobic axenic culture and in the high-dose aerosol mouse model, quantification of\n                    <jats:italic>Mtb<\/jats:italic>\n                    rRNA synthesis via the RS ratio and\n                    <jats:italic>Mtb<\/jats:italic>\n                    transcriptional profiling via SEARCH-TB revealed that longer drug exposure was associated with greater injury and adaptation during treatment, as well as slower recovery after treatment,\n                    <jats:italic>i.e.,<\/jats:italic>\n                    longer PAE. Recovery followed a conserved sequence, from resumption of rRNA synthesis, to broad transcriptional reprogramming, to eventual CFU change. In mice, however, physiologic recovery was markedly slower and less complete than\n                    <jats:italic>in vitro<\/jats:italic>\n                    , indicating longer PAE in the context of immunity. Our observation that PAE in\n                    <jats:italic>Mtb<\/jats:italic>\n                    depends on the duration of drug exposure and correlates with the degree of bacterial injury support the hypothesis that nonlethal physiologic damage contributes to PAE. Our observation that PAE of the standard TB regimen is longer in mice than\n                    <jats:italic>in vitro<\/jats:italic>\n                    indicates that immunity augments PAE for\n                    <jats:italic>Mtb<\/jats:italic>\n                    . Molecular evaluation of bacterial physiology provides a new basis for probing recovery from drug exposure and understanding PAE.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1014131","type":"journal-article","created":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T17:38:12Z","timestamp":1776879492000},"page":"e1014131","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Physiologic recovery of Mycobacterium tuberculosis from drug injury: A molecular study of post antibiotic effect in vitro and in vivo"],"prefix":"10.1371","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9029-2390","authenticated-orcid":true,"given":"Jo","family":"Hendrix","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reem","family":"Al Mubarak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew J.","family":"Reichlen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel T.","family":"Tabor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adeline","family":"Bateman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa M.","family":"Massoudi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Rossmassler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Firat","family":"Kaya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew D.","family":"Zimmerman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Holly","family":"Nielsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth A.","family":"Wynn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin I.","family":"Voskuil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory T.","family":"Robertson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camille M.","family":"Moore","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0126-1993","authenticated-orcid":true,"given":"Nicholas D.","family":"Walter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,4,22]]},"reference":[{"key":"ppat.1014131.ref001","unstructured":"WHO. Global tuberculosis report 2024. https:\/\/www.who.int\/publications\/i\/item\/9789240101531"},{"key":"ppat.1014131.ref002","doi-asserted-by":"crossref","first-page":"3631","DOI":"10.1128\/AAC.45.12.3631-3634.2001","article-title":"Postantibiotic effects of antituberculosis agents alone and in combination","volume":"45","author":"CY Chan","year":"2001","journal-title":"Antimicrob Agents Chemother"},{"issue":"4","key":"ppat.1014131.ref003","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1093\/jac\/32.4.519","article-title":"The post-antibiotic effect","volume":"32","author":"FM MacKenzie","year":"1993","journal-title":"J Antimicrob Chemother"},{"key":"ppat.1014131.ref004","unstructured":"WHO. 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