99182 20210902121937.0 doi 10.1371/journal.ppat.1009061 sideral 122683 ART-2020-122683 eng Mata, E. Universidad de Zaragoza Independent genomic polymorphisms in the PknH serine threonine kinase locus during evolution of the Mycobacterium tuberculosis Complex affect virulence and host preference 2020 Access copy available to the general public Unrestricted Species belonging to the Mycobacterium tuberculosis Complex (MTBC) show more than 99% genetic identity but exhibit distinct host preference and virulence. The molecular genetic changes that underly host specificity and infection phenotype within MTBC members have not been fully elucidated. Here, we analysed RD900 genomic region across MTBC members using whole genome sequences from 60 different MTBC strains so as to determine its role in the context of MTBC evolutionary history. The RD900 region comprises two homologous genes, pknH1 and pknH2, encoding a serine/threonine protein kinase PknH flanking the tbd2 gene. Our analysis revealed that RD900 has been independently lost in different MTBC lineages and different strains, resulting in the generation of a single pknH gene. Importantly, all the analysed M. bovis and M. caprae strains carry a conserved deletion within a proline rich-region of pknH, independent of the presence or absence of RD900. We hypothesized that deletion of pknH proline rich-region in M. bovis may affect PknH function, having a potential role in its virulence and evolutionary adaptation. To explore this hypothesis, we constructed two M. bovis ‘knock-in’ strains containing the M. tuberculosis pknH gene. Evaluation of their virulence phenotype in mice revealed a reduced virulence of both M. bovis knock-in strains compared to the wild type, suggesting that PknH plays an important role in the differential virulence phenotype of M. bovis vs M. tuberculosis. info:eu-repo/grantAgreement/ES/MCIU/RTI2018-097625-B-I00 info:eu-repo/semantics/openAccess by http://creativecommons.org/licenses/by/3.0/es/ 6.823 2020 MICROBIOLOGY 20 / 136 = 0.147 2020 Q1 T1 VIROLOGY 7 / 36 = 0.194 2020 Q1 T1 PARASITOLOGY 3 / 38 = 0.079 2020 Q1 T1 3.718 2020 Genetics 2020 Q1 Immunology 2020 Q1 Virology 2020 Q1 Molecular Biology 2020 Q1 Parasitology 2020 Q1 Microbiology 2020 Q1 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Farrell, D. Ma, R. Uranga, S. Universidad de Zaragoza (orcid)0000-0001-7866-2803 Gomez, A.B. Universidad de Zaragoza (orcid)0000-0002-9713-2127 Monzon, M. Universidad de Zaragoza (orcid)0000-0002-2787-9671 Badiola, J. Universidad de Zaragoza (orcid)0000-0002-7173-7216 Anel, A. Universidad de Zaragoza (orcid)0000-0002-5175-8394 Gonzalo-Asensio, J. Universidad de Zaragoza (orcid)0000-0001-8841-6593 Martin, C. Universidad de Zaragoza (orcid)0000-0003-2993-5478 Gordon, S.V. Aguilo, N. Universidad de Zaragoza (orcid)0000-0001-7897-9173 1011 630 Universidad de Zaragoza Dpto. Microb.Ped.Radio.Sal.Pú. Área Microbiología 1003 443 Universidad de Zaragoza Dpto. Anatom.Histolog.Humanas Area Histología 1009 773 Universidad de Zaragoza Dpto. Patología Animal Área Sanidad Animal 1011 X Universidad de Zaragoza Dpto. Microb.Ped.Radio.Sal.Pú. Proy. investigación HQA 1002 060 Universidad de Zaragoza Dpto. Bioq.Biolog.Mol. Celular Área Bioquímica y Biolog.Mole. 16, 12 (2020), e1009061[24 pp] PLoS Pathog. PLoS Pathogens 1553-7366 756355 http://zaguan.unizar.es/record/99182/files/texto_completo.pdf Versión publicada 2401917 http://zaguan.unizar.es/record/99182/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:99182 articulos driver 2021-09-02-10:58:52 ARTICLE