{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T23:04:22Z","timestamp":1787353462872,"version":"build-2736575974"},"reference-count":49,"publisher":"American Society for Microbiology","issue":"7","license":[{"start":{"date-parts":[[2018,7,1]],"date-time":"2018-07-01T00:00:00Z","timestamp":1530403200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"Innovative Medicines Initiative Joint Undertaking","award":["115337"],"award-info":[{"award-number":["115337"]}]},{"name":"Netherlands Organization for Scientific Research","award":["016.Veni.171.090"],"award-info":[{"award-number":["016.Veni.171.090"]}]},{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["1DP2LM011952"],"award-info":[{"award-number":["1DP2LM011952"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["T32 AI 7329-23"],"award-info":[{"award-number":["T32 AI 7329-23"]}],"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":[[2018,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Due to the rise of drug-resistant forms of tuberculosis, there is an urgent need for novel antibiotics to effectively combat these cases and shorten treatment regimens. Recently, drug screens using whole-cell analyses have been shown to be successful. However, current high-throughput screens focus mostly on\n                    <jats:italic>stricto sensu<\/jats:italic>\n                    life\/death screening that give little qualitative information. In doing so, promising compound scaffolds or nonoptimized compounds that fail to reach inhibitory concentrations are missed. To accelerate early tuberculosis (TB) drug discovery, we performed RNA sequencing on\n                    <jats:named-content content-type=\"genus-species\">Mycobacterium tuberculosis<\/jats:named-content>\n                    and\n                    <jats:named-content content-type=\"genus-species\">Mycobacterium marinum<\/jats:named-content>\n                    to map the stress responses that follow upon exposure to subinhibitory concentrations of antibiotics with known targets, ciprofloxacin, ethambutol, isoniazid, streptomycin, and rifampin. The resulting data set comprises the first overview of transcriptional stress responses of mycobacteria to different antibiotics. We show that antibiotics can be distinguished based on their specific transcriptional stress fingerprint. Notably, this fingerprint was more distinctive in\n                    <jats:named-content content-type=\"genus-species\">M. marinum<\/jats:named-content>\n                    . We decided to use this to our advantage and continue with this model organism. A selection of diverse antibiotic stress genes was used to construct stress reporters. In total, three functional reporters were constructed to respond to DNA damage, cell wall damage, and ribosomal inhibition. Subsequently, these reporter strains were used to screen a small anti-TB compound library to predict the mode of action. In doing so, we identified the putative modes of action for three novel compounds, which confirms the utility of our approach.\n                  <\/jats:p>","DOI":"10.1128\/aac.00083-18","type":"journal-article","created":{"date-parts":[[2018,4,13]],"date-time":"2018-04-13T06:37:21Z","timestamp":1523601441000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":20,"title":["Accelerating Early Antituberculosis Drug Discovery by Creating Mycobacterial Indicator Strains That Predict Mode of Action"],"prefix":"10.1128","volume":"62","author":[{"given":"Maikel","family":"Boot","sequence":"first","affiliation":[{"name":"Department of Medical Microbiology and Infection Control, VU University Medical Center, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanna","family":"Commandeur","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Infection Control, VU University Medical Center, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amit K.","family":"Subudhi","sequence":"additional","affiliation":[{"name":"Division of Biological and Environmental Sciences and Engineering, King Abdullah University of Science and Technology (KAUST), Thuwal, Kingdom of Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meriem","family":"Bahira","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"II","given":"Trever C.","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdallah M.","family":"Abdallah","sequence":"additional","affiliation":[{"name":"Division of Biological and Environmental Sciences and Engineering, King Abdullah University of Science and Technology (KAUST), Thuwal, Kingdom of Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mae","family":"van Gemert","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Infection Control, VU University Medical Center, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jo\u00ebl","family":"Leli\u00e8vre","sequence":"additional","affiliation":[{"name":"Diseases of the Developing World, GlaxoSmithKline, Tres Cantos, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Llu\u00eds","family":"Ballell","sequence":"additional","affiliation":[{"name":"Diseases of the Developing World, GlaxoSmithKline, Tres Cantos, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bree B.","family":"Aldridge","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnab","family":"Pain","sequence":"additional","affiliation":[{"name":"Division of Biological and Environmental Sciences and Engineering, King Abdullah University of Science and Technology (KAUST), Thuwal, Kingdom of Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Speer","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Infection Control, VU University Medical Center, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wilbert","family":"Bitter","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Infection Control, VU University Medical Center, Amsterdam, The Netherlands"},{"name":"Department of Molecular Microbiology, VU University, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","volume-title":"Global tuberculosis report 2017","author":"World Health Organization","year":"2017","unstructured":"World Health Organization. 2017. 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