{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T05:27:04Z","timestamp":1790832424254,"version":"4.1.0"},"reference-count":59,"publisher":"American Society for Microbiology","issue":"3","license":[{"start":{"date-parts":[[2014,5,20]],"date-time":"2014-05-20T00:00:00Z","timestamp":1400544000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-sa\/3.0\/"},{"start":{"date-parts":[[2014,7,1]],"date-time":"2014-07-01T00:00:00Z","timestamp":1404172800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2014,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Strong evidence supports the idea that fatty acids rather than carbohydrates are the main energy source of\n                    <jats:named-content content-type=\"genus-species\">Mycobacterium tuberculosis<\/jats:named-content>\n                    during infection and latency. Despite that important role, a complete scenario of the bacterium\u2019s metabolism when lipids are the main energy source is still lacking. Here we report the development of an\n                    <jats:italic>in vitro<\/jats:italic>\n                    model to analyze adaptation of\n                    <jats:named-content content-type=\"genus-species\">M. tuberculosis<\/jats:named-content>\n                    during\u00a0assimilation of long-chain fatty acids as sole carbon sources. The global lipid transcriptome revealed a shift toward the glyoxylate cycle, the overexpression of main regulators\n                    <jats:italic>whiB3<\/jats:italic>\n                    ,\n                    <jats:italic>dosR<\/jats:italic>\n                    , and Rv0081, and the increased expression of several genes related to reductive stress. Our evidence showed that lipid storage seems to be the selected mechanism used by\n                    <jats:named-content content-type=\"genus-species\">M. tuberculosis<\/jats:named-content>\n                    to ameliorate the assumed damage of reductive stress and that concomitantly the bacilli acquired a slowed-growth and drug-tolerant phenotype, all characteristics previously associated with the dormant stage. Additionally, intergenic regions were also detected, including the unexpected upregulation of tRNAs that suggest a new role for these molecules in the acquisition of a drug-tolerant phenotype by dormant bacilli. Finally, a set of lipid signature\u00a0genes for the\u00a0adaptation process was also identified. This\n                    <jats:italic>in vitro<\/jats:italic>\n                    model represents a suitable condition to illustrate the participation of reductive stress in drugs\u2019 activity against dormant bacilli, an aspect scarcely investigated to date. This approach provides a new perspective to the understanding of latent infection and suggests the participation of previously undetected molecules.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>IMPORTANCE<\/jats:bold>\n                    <jats:named-content content-type=\"genus-species\">Mycobacterium tuberculosis<\/jats:named-content>\n                    establishes long-lasting highly prevalent infection inside the human body, called latent tuberculosis. The known involvement of fatty acids is changing our understanding of that silent infection; however, question of how tubercle bacilli globally adapt to a lipid-enriched environment is still an unanswered. With the single change of providing fatty acids as carbon sources, the bacilli switch on their program related to dormant stage: slowed growth, accumulation of lipid bodies, and development of drug tolerance. In this stage, unexpected and previously unknown participants were found to play putatively important roles during the process. For the first time, this work compares the global transcriptomics of bacteria by using strand-specific RNA sequencing under two different growth conditions. This study suggests novel targets for the control of tuberculosis and provides a new straightforward\n                    <jats:italic>in vitro<\/jats:italic>\n                    model that could help to test the activity of drugs against dormant bacilli from a novel perspective.\n                  <\/jats:p>","DOI":"10.1128\/mbio.01125-14","type":"journal-article","created":{"date-parts":[[2014,5,21]],"date-time":"2014-05-21T01:59:11Z","timestamp":1400637551000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":109,"title":["Global Adaptation to a Lipid Environment Triggers the Dormancy-Related Phenotype of Mycobacterium tuberculosis"],"prefix":"10.1128","volume":"5","author":[{"given":"Juan G.","family":"Rodr\u00edguez","sequence":"first","affiliation":[{"name":"Departamento de Biotecnolog\u00eda Molecular y Gen\u00e9tica Molecular, Corporaci\u00f3n CorpoGen, Bogot\u00e1, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriana C.","family":"Hern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Departamento de Biotecnolog\u00eda Molecular y Gen\u00e9tica Molecular, Corporaci\u00f3n CorpoGen, Bogot\u00e1, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecilia","family":"Helguera-Repetto","sequence":"additional","affiliation":[{"name":"Escuela Nacional de Ciencias Biol\u00f3gicas, Instituto Polit\u00e9cnico Nacional (IPN), Mexico Distrito Federal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana","family":"Aguilar Ayala","sequence":"additional","affiliation":[{"name":"Escuela Nacional de Ciencias Biol\u00f3gicas, Instituto Polit\u00e9cnico Nacional (IPN), Mexico Distrito Federal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosalina","family":"Guadarrama-Medina","sequence":"additional","affiliation":[{"name":"Escuela Nacional de Ciencias Biol\u00f3gicas, Instituto Polit\u00e9cnico Nacional (IPN), Mexico Distrito Federal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan M.","family":"Anz\u00f3la","sequence":"additional","affiliation":[{"name":"Departamento de Biotecnolog\u00eda Molecular y Gen\u00e9tica Molecular, Corporaci\u00f3n CorpoGen, Bogot\u00e1, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose R.","family":"Bustos","sequence":"additional","affiliation":[{"name":"Departamento de Biotecnolog\u00eda Molecular y Gen\u00e9tica Molecular, Corporaci\u00f3n CorpoGen, Bogot\u00e1, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda M.","family":"Zambrano","sequence":"additional","affiliation":[{"name":"Departamento de Biotecnolog\u00eda Molecular y Gen\u00e9tica Molecular, Corporaci\u00f3n CorpoGen, Bogot\u00e1, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge","family":"Gonz\u00e1lez-y-Merchand","sequence":"additional","affiliation":[{"name":"Escuela Nacional de Ciencias Biol\u00f3gicas, Instituto Polit\u00e9cnico Nacional (IPN), Mexico Distrito Federal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda J.","family":"Garc\u00eda","sequence":"additional","affiliation":[{"name":"Departamento de Medicina Preventiva, Facultad de Medicina, Universidad Aut\u00f3noma de Madrid, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Del Portillo","sequence":"additional","affiliation":[{"name":"Departamento de Biotecnolog\u00eda Molecular y Gen\u00e9tica Molecular, Corporaci\u00f3n CorpoGen, Bogot\u00e1, 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