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While antibiotic-treated\n              <jats:italic>Mtb<\/jats:italic>\n              has been evaluated in\n              <jats:italic>in vitro<\/jats:italic>\n              experiments\n              <jats:italic>,<\/jats:italic>\n              it is unclear if and how long-term\n              <jats:italic>in vivo<\/jats:italic>\n              treatment with diverse antibiotics with varying treatment-shortening activity (sterilizing activity) affects\n              <jats:italic>Mtb<\/jats:italic>\n              physiologic processes differently. Here, we used SEARCH-TB, a pathogen-targeted RNA-sequencing platform, to characterize the\n              <jats:italic>Mtb<\/jats:italic>\n              transcriptome in the BALB\/c high-dose aerosol infection mouse model following 4 weeks of treatment with three sterilizing and three non-sterilizing antibiotics. Certain transcriptional changes were shared among most antibiotics, including decreased expression of genes associated with protein synthesis and metabolism and the induction of certain genes associated with stress responses. However, the magnitude of this shared response differed between antibiotics. Sterilizing antibiotics rifampin, pyrazinamide, and bedaquiline generated a more quiescent\n              <jats:italic>Mtb<\/jats:italic>\n              state than did non-sterilizing antibiotics isoniazid, ethambutol, and streptomycin, as indicated by the decreased expression of genes associated with translation, transcription, secretion of immunogenic proteins, metabolism, and cell wall synthesis. Additionally, we identified distinguishing transcriptional effects specific to each antibiotic, indicating that different mechanisms of action induce distinct patterns in response to cellular injury. In addition to elucidating the\n              <jats:italic>Mtb<\/jats:italic>\n              physiologic changes associated with antibiotic stress, this study demonstrates the value of SEARCH-TB as a highly granular pharmacodynamic assay that reveals antibiotic effects that are not apparent based on culture alone.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/aac.01310-24","type":"journal-article","created":{"date-parts":[[2025,1,17]],"date-time":"2025-01-17T14:00:42Z","timestamp":1737122442000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":6,"title":["Emergence of antibiotic-specific\n            <i>Mycobacterium tuberculosis<\/i>\n            phenotypes during prolonged treatment of mice"],"prefix":"10.1128","volume":"69","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5857-4483","authenticated-orcid":false,"given":"Elizabeth A.","family":"Wynn","sequence":"first","affiliation":[{"name":"Rocky Mountain Regional VA Medical Center","place":["Aurora, USA"]},{"name":"Center for Genes, Environment and Health, National Jewish Health","place":["Denver, USA"]},{"name":"Consortium for Applied Microbial Metrics","place":["Aurora, USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9854-1785","authenticated-orcid":true,"given":"Christian","family":"Dide-Agossou","sequence":"additional","affiliation":[{"name":"Rocky Mountain Regional VA Medical Center","place":["Aurora, USA"]},{"name":"Consortium for Applied Microbial Metrics","place":["Aurora, USA"]},{"name":"Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado Anschutz Medical Campus","place":["Aurora, USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Reem","family":"Al Mubarak","sequence":"additional","affiliation":[{"name":"Rocky Mountain Regional VA Medical Center","place":["Aurora, USA"]},{"name":"Consortium for Applied Microbial Metrics","place":["Aurora, USA"]},{"name":"Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado Anschutz Medical Campus","place":["Aurora, USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karen","family":"Rossmassler","sequence":"additional","affiliation":[{"name":"Rocky Mountain Regional VA Medical Center","place":["Aurora, USA"]},{"name":"Consortium for Applied Microbial Metrics","place":["Aurora, USA"]},{"name":"Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado Anschutz Medical Campus","place":["Aurora, USA"]},{"name":"Linda Crnic Institute for Down Syndrome, University of Colorado Anschutz Medical Campus","place":["Aurora, USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Victoria","family":"Ektnitphong","sequence":"additional","affiliation":[{"name":"Mycobacteria Research Laboratories, Department of Microbiology, Immunology, and Pathology, Colorado State University","place":["Fort Collins, USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Allison A.","family":"Bauman","sequence":"additional","affiliation":[{"name":"Mycobacteria Research Laboratories, Department of Microbiology, Immunology, and Pathology, Colorado State University","place":["Fort Collins, USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisa M.","family":"Massoudi","sequence":"additional","affiliation":[{"name":"Mycobacteria Research Laboratories, Department of Microbiology, Immunology, and Pathology, Colorado State University","place":["Fort Collins, USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin I.","family":"Voskuil","sequence":"additional","affiliation":[{"name":"Consortium for Applied Microbial Metrics","place":["Aurora, USA"]},{"name":"Department of Immunology and Microbiology, University of Colorado Anschutz Medical Campus","place":["Aurora, USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7157-4034","authenticated-orcid":true,"given":"Gregory T.","family":"Robertson","sequence":"additional","affiliation":[{"name":"Consortium for Applied Microbial Metrics","place":["Aurora, USA"]},{"name":"Mycobacteria Research Laboratories, Department of Microbiology, Immunology, and Pathology, Colorado State University","place":["Fort Collins, USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Camille M.","family":"Moore","sequence":"additional","affiliation":[{"name":"Center for Genes, Environment and Health, National Jewish Health","place":["Denver, USA"]},{"name":"Consortium for Applied Microbial Metrics","place":["Aurora, USA"]},{"name":"Department of Biostatistics and Informatics, University of Colorado Anschutz Medical Campus","place":["Aurora, USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0126-1993","authenticated-orcid":true,"given":"Nicholas D.","family":"Walter","sequence":"additional","affiliation":[{"name":"Rocky Mountain Regional VA Medical Center","place":["Aurora, USA"]},{"name":"Consortium for Applied Microbial Metrics","place":["Aurora, USA"]},{"name":"Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado Anschutz Medical Campus","place":["Aurora, USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_5_2_2","unstructured":"World Health Organization. 2024. 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