165910 20260116002211.0 doi 10.1371/journal.pone.0045213 sideral 78879 ART-2012-78879 eng Aporta, A. Universidad de Zaragoza Attenuated Mycobacterium tuberculosis SO2 Vaccine Candidate Is Unable to Induce Cell Death 2012 t has been proposed that Mycobacterium tuberculosis virulent strains inhibit apoptosis and trigger cell death by necrosis of host macrophages to evade innate immunity, while non-virulent strains induce typical apoptosis activating a protective host response. As part of the characterization of a novel tuberculosis vaccine candidate, the M. tuberculosis phoP mutant SO2, we sought to evaluate its potential to induce host cell death. The parental M. tuberculosis MT103 strain and the current vaccine against tuberculosis Bacillus Calmette-Guérin (BCG) were used as comparators in mouse models in vitro and in vivo. Our data reveal that attenuated SO2 was unable to induce apoptotic events neither in mouse macrophages in vitro nor during lung infection in vivo. In contrast, virulent MT103 triggers typical apoptotic events with phosphatidylserine exposure, caspase-3 activation and nuclear condensation and fragmentation. BCG strain behaved like SO2 and did not induce apoptosis. A clonogenic survival assay confirmed that viability of BCG- or SO2-infected macrophages was unaffected. Our results discard apoptosis as the protective mechanism induced by SO2 vaccine and provide evidence for positive correlation between classical apoptosis induction and virulent strains, suggesting apoptosis as a possible virulence determinant during M. tuberculosis infection. Access copy available to the general public Unrestricted info:eu-repo/semantics/openAccess by https://creativecommons.org/licenses/by/4.0/deed.es 3.73 2012 MULTIDISCIPLINARY SCIENCES 7 / 57 = 0.123 2012 Q1 T1 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Arbues, A. (orcid)0000-0002-3377-4171 Aguilo, J. I. Universidad de Zaragoza (orcid)0000-0001-7897-9173 Monzon, M. Universidad de Zaragoza (orcid)0000-0002-2787-9671 Badiola, J. J. Universidad de Zaragoza (orcid)0000-0002-7173-7216 de Martino, A. Ferrer, N. Marinova, D. Anel, A. Universidad de Zaragoza (orcid)0000-0002-5175-8394 Martin, C. Universidad de Zaragoza (orcid)0000-0003-2993-5478 Pardo, J. Universidad de Zaragoza (orcid)0000-0003-0154-0730 1008 630 Universidad de Zaragoza Dpto. Microb.Med.Pr.,Sal.Públ. Área Microbiología 1009 773 Universidad de Zaragoza Dpto. Patología Animal Área Sanidad Animal 1008 566 Universidad de Zaragoza Dpto. Microb.Med.Pr.,Sal.Públ. Área Inmunología 1002 X Universidad de Zaragoza Dpto. Bioq.Biolog.Mol. Celular Proy. investigación DEA 1002 060 Universidad de Zaragoza Dpto. Bioq.Biolog.Mol. Celular Área Bioquímica y Biolog.Mole. 7, 9 (2012), e45213 [11 pp.] PLoS One PLoS ONE 1932-6203 4624017 http://zaguan.unizar.es/record/165910/files/texto_completo.pdf Versión publicada 3359602 http://zaguan.unizar.es/record/165910/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:165910 articulos driver 2026-01-15-21:56:24 ARTICLE