{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T11:29:41Z","timestamp":1787830181687,"version":"build-2784847793"},"reference-count":44,"publisher":"American Society for Microbiology","issue":"3","license":[{"start":{"date-parts":[[2016,5,24]],"date-time":"2016-05-24T00:00:00Z","timestamp":1464048000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2016,7,6]],"date-time":"2016-07-06T00:00:00Z","timestamp":1467763200000},"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":[[2016,7,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The current tuberculosis (TB) vaccine,\n                    <jats:named-content content-type=\"genus-species\">Mycobacterium bovis<\/jats:named-content>\n                    Bacillus Calmette-Gu\u00e9rin (BCG), provides insufficient protection against pulmonary TB. Previously, we generated a listeriolysin-expressing recombinant BCG strain, which to date has successfully completed phase I and phase IIa clinical trials. In an attempt to further improve efficacy, we deleted the antiapoptotic virulence gene\n                    <jats:italic>nuoG<\/jats:italic>\n                    , encoding NADH dehydrogenase 1 subunit G, from BCG \u0394\n                    <jats:italic>ureC<\/jats:italic>\n                    ::\n                    <jats:italic>hly<\/jats:italic>\n                    .\n                    <jats:italic>In vitro<\/jats:italic>\n                    , deletion of\n                    <jats:italic>nuoG<\/jats:italic>\n                    unexpectedly led to strongly increased recruitment of the autophagosome marker LC3 to the engulfed vaccine, suggesting that\n                    <jats:italic>nuoG<\/jats:italic>\n                    also affects xenophagic pathways. In mice, BCG \u0394\n                    <jats:italic>ureC<\/jats:italic>\n                    ::\n                    <jats:italic>hly<\/jats:italic>\n                    \u0394\n                    <jats:italic>nuoG<\/jats:italic>\n                    vaccination was safer than BCG and improved protection over that of parental BCG \u0394\n                    <jats:italic>ureC<\/jats:italic>\n                    ::\n                    <jats:italic>hly<\/jats:italic>\n                    , significantly reducing TB load in murine lungs, ameliorating pulmonary pathology, and enhancing immune responses. Transcriptome analysis of draining lymph nodes after vaccination with either BCG \u0394\n                    <jats:italic>ureC<\/jats:italic>\n                    ::\n                    <jats:italic>hly<\/jats:italic>\n                    or BCG \u0394\n                    <jats:italic>ureC<\/jats:italic>\n                    ::\n                    <jats:italic>hly<\/jats:italic>\n                    \u0394\n                    <jats:italic>nuoG<\/jats:italic>\n                    demonstrated earlier and stronger induction of immune responses than that with BCG SSI and suggested upregulation of inflammasome activation and interferon-induced GTPases. In summary, BCG \u0394\n                    <jats:italic>ureC<\/jats:italic>\n                    ::\n                    <jats:italic>hly<\/jats:italic>\n                    \u0394\n                    <jats:italic>nuoG<\/jats:italic>\n                    is a promising next-generation TB vaccine candidate with excellent efficacy and safety.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>IMPORTANCE<\/jats:bold>\n                    Autophagy and apoptosis are fundamental processes allowing cells to degrade their components or kill themselves, respectively. The immune system has adopted these mechanisms to eliminate intracellular pathogens. Residing in host cells, the causative agent of tuberculosis,\n                    <jats:named-content content-type=\"genus-species\">Mycobacterium tuberculosis<\/jats:named-content>\n                    , has evolved strategies to set cellular programs of autophagy and apoptosis \u201con hold.\u201d The mycobacterial gene\n                    <jats:italic>nuoG<\/jats:italic>\n                    was found to prevent host cell apoptosis. We have deleted\n                    <jats:italic>nuoG<\/jats:italic>\n                    in the live vaccine candidate BCG \u0394\n                    <jats:italic>ureC<\/jats:italic>\n                    ::\n                    <jats:italic>hly<\/jats:italic>\n                    , which is in phase II clinical development, to leave cellular apoptosis \u201con go\u201d upon immunization. In preclinical models, this strategy boosted immunity and improved protection from\n                    <jats:named-content content-type=\"genus-species\">M. tuberculosis<\/jats:named-content>\n                    infection. Unexpectedly, we obtained compelling evidence that mycobacterial\n                    <jats:italic>nuoG<\/jats:italic>\n                    facilitates inhibition of autophagic pathways, suggesting a new role for this gene in the host-pathogen interplay in tuberculosis.\n                  <\/jats:p>","DOI":"10.1128\/mbio.00679-16","type":"journal-article","created":{"date-parts":[[2016,5,24]],"date-time":"2016-05-24T21:13:40Z","timestamp":1464124420000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":79,"title":["Deletion of\n                    <i>nuoG<\/i>\n                    from the Vaccine Candidate Mycobacterium bovis BCG \u0394\n                    <i>ureC<\/i>\n                    ::\n                    <i>hly<\/i>\n                    Improves Protection against Tuberculosis"],"prefix":"10.1128","volume":"7","author":[{"given":"Martin","family":"Gengenbacher","sequence":"first","affiliation":[{"name":"Department of Immunology, Max Planck Institute for Infection Biology, Berlin, Germany"},{"name":"Department of Microbiology and Immunology, National University of Singapore, Yong Loo Lin School of Medicine, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalie","family":"Nieuwenhuizen","sequence":"additional","affiliation":[{"name":"Department of Immunology, Max Planck Institute for Infection Biology, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexis","family":"Vogelzang","sequence":"additional","affiliation":[{"name":"Department of Immunology, Max Planck Institute for Infection Biology, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haipeng","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Immunology, Max Planck Institute for Infection Biology, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peggy","family":"Kaiser","sequence":"additional","affiliation":[{"name":"Department of Immunology, Max Planck Institute for Infection Biology, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefanie","family":"Schuerer","sequence":"additional","affiliation":[{"name":"Department of Immunology, Max Planck Institute for Infection Biology, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Doris","family":"Lazar","sequence":"additional","affiliation":[{"name":"Department of Immunology, Max Planck Institute for Infection Biology, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ina","family":"Wagner","sequence":"additional","affiliation":[{"name":"Max Planck Institute for Infection Biology, Core Facility Genomics\/Microarray, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans-Joachim","family":"Mollenkopf","sequence":"additional","affiliation":[{"name":"Max Planck Institute for Infection Biology, Core Facility Genomics\/Microarray, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan H. 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