{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T08:47:36Z","timestamp":1790844456274,"version":"4.1.0"},"reference-count":36,"publisher":"American Society for Microbiology","issue":"7","license":[{"start":{"date-parts":[[2017,7,1]],"date-time":"2017-07-01T00:00:00Z","timestamp":1498867200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["R21 AI110078"],"award-info":[{"award-number":["R21 AI110078"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2017,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Tuberculosis (TB) continues to be one of the most common bacterial infectious diseases and is the leading cause of death in many parts of the world. A major limitation of TB therapy is slow killing of the infecting organism, increasing the risk for the development of a tolerance phenotype and drug resistance. Studies indicate that\n            <jats:named-content content-type=\"genus-species\">Mycobacterium tuberculosis<\/jats:named-content>\n            takes several days to be killed upon treatment with lethal concentrations of antibiotics both\n            <jats:italic>in vitro<\/jats:italic>\n            and\n            <jats:italic>in vivo<\/jats:italic>\n            . To investigate how metabolic remodeling can enable transient bacterial survival during exposure to bactericidal concentrations of compounds,\n            <jats:named-content content-type=\"genus-species\">M. tuberculosis<\/jats:named-content>\n            strain H37Rv was exposed to twice the MIC of isoniazid, rifampin, moxifloxacin, mefloquine, or bedaquiline for 24 h, 48 h, 4 days, and 6 days, and the bacterial proteomic response was analyzed using quantitative shotgun mass spectrometry. Numerous sets of\n            <jats:italic>de novo<\/jats:italic>\n            bacterial proteins were identified over the 6-day treatment. Network analysis and comparisons between the drug treatment groups revealed several shared sets of predominant proteins and enzymes simultaneously belonging to a number of diverse pathways. Overexpression of some of these proteins in the nonpathogenic\n            <jats:named-content content-type=\"genus-species\">Mycobacterium smegmatis<\/jats:named-content>\n            extended bacterial survival upon exposure to bactericidal concentrations of antimicrobials, and inactivation of some proteins in\n            <jats:named-content content-type=\"genus-species\">M. tuberculosis<\/jats:named-content>\n            prevented the pathogen from escaping the fast killing\n            <jats:italic>in vitro<\/jats:italic>\n            and in macrophages, as well. Our biology-driven approach identified promising bacterial metabolic pathways and enzymes that might be targeted by novel drugs to reduce the length of tuberculosis therapy.\n          <\/jats:p>","DOI":"10.1128\/aac.00430-17","type":"journal-article","created":{"date-parts":[[2017,4,18]],"date-time":"2017-04-18T00:55:21Z","timestamp":1492476921000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":30,"title":["Mycobacterium tuberculosis Proteome Response to Antituberculosis Compounds Reveals Metabolic \u201cEscape\u201d Pathways That Prolong Bacterial Survival"],"prefix":"10.1128","volume":"61","author":[{"given":"Lia","family":"Danelishvili","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences, College of Veterinary Medicine, Oregon State University, Corvallis, Oregon, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Shulzhenko","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, College of Veterinary Medicine, Oregon State University, Corvallis, Oregon, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica J. J.","family":"Chinison","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, College of Veterinary Medicine, Oregon State University, Corvallis, Oregon, USA"},{"name":"Department of Microbiology, College of Science, Oregon State University, Corvallis, Oregon, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lmar","family":"Babrak","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, College of Veterinary Medicine, Oregon State University, Corvallis, Oregon, USA"},{"name":"Department of Microbiology, College of Science, Oregon State University, Corvallis, Oregon, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jialu","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Corvallis, Oregon, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andriy","family":"Morgun","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Corvallis, Oregon, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory","family":"Burrows","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Oregon Health and Science University, Portland, Oregon, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luiz E.","family":"Bermudez","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, College of Veterinary Medicine, Oregon State University, Corvallis, Oregon, USA"},{"name":"Department of Microbiology, College of Science, Oregon State University, Corvallis, Oregon, 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