{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T02:52:09Z","timestamp":1792637529296,"version":"4.5.0"},"reference-count":51,"publisher":"American Society for Microbiology","issue":"6","license":[{"start":{"date-parts":[[2018,6,1]],"date-time":"2018-06-01T00:00:00Z","timestamp":1527811200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01-AI110780"],"award-info":[{"award-number":["R01-AI110780"]}],"id":[{"id":"10.13039\/100000060","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":[[2018,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    <jats:named-content content-type=\"genus-species\">Mycobacterium tuberculosis<\/jats:named-content>\n                    is a critical threat to human health due to the increased prevalence of rifampin resistance (RMP\n                    <jats:sup>r<\/jats:sup>\n                    ). Fitness defects have been observed in RMP\n                    <jats:sup>r<\/jats:sup>\n                    mutants with amino acid substitutions in the \u03b2 subunit of RNA polymerase (RNAP). In clinical isolates, this fitness defect can be ameliorated by the presence of secondary mutations in the double-psi \u03b2-barrel (DPBB) domain of the \u03b2\u2032 subunit of RNAP. To identify factors contributing to the fitness defects observed\n                    <jats:italic>in vivo<\/jats:italic>\n                    , several\n                    <jats:italic>in vitro<\/jats:italic>\n                    RNA transcription assays were utilized to probe initiation, elongation, termination, and 3\u2032-RNA hydrolysis with the wild-type and RMP\n                    <jats:sup>r<\/jats:sup>\n                    <jats:named-content content-type=\"genus-species\">M. tuberculosis<\/jats:named-content>\n                    RNAPs. We found that the less prevalent RMP\n                    <jats:sup>r<\/jats:sup>\n                    mutants exhibit significantly poorer termination efficiencies relative to the wild type, an important factor for proper gene expression. We also found that several mechanistic aspects of transcription of the RMP\n                    <jats:sup>r<\/jats:sup>\n                    mutant RNAPs are impacted relative to the wild type. For the clinically most prevalent mutant, the \u03b2S450L mutant, these defects are mitigated by the presence of secondary\/compensatory mutations in the DPBB domain of the \u03b2\u2032 subunit.\n                  <\/jats:p>","DOI":"10.1128\/aac.00164-18","type":"journal-article","created":{"date-parts":[[2018,4,11]],"date-time":"2018-04-11T08:11:56Z","timestamp":1523434316000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":44,"title":["Source of the Fitness Defect in Rifamycin-Resistant Mycobacterium tuberculosis RNA Polymerase and the Mechanism of Compensation by Mutations in the \u03b2\u2032 Subunit"],"prefix":"10.1128","volume":"62","author":[{"given":"Maxwell A.","family":"Stefan","sequence":"first","affiliation":[{"name":"Department of Medicinal Chemistry, University of Michigan, Ann Arbor, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatima S.","family":"Ugur","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, University of Michigan, Ann Arbor, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George A.","family":"Garcia","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, University of Michigan, Ann Arbor, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","volume-title":"Global tuberculosis report 2016","author":"World Health Organization","year":"2016","unstructured":"World Health Organization. 2016. 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