000099182 001__ 99182 000099182 005__ 20210902121937.0 000099182 0247_ $$2doi$$a10.1371/journal.ppat.1009061 000099182 0248_ $$2sideral$$a122683 000099182 037__ $$aART-2020-122683 000099182 041__ $$aeng 000099182 100__ $$aMata, E.$$uUniversidad de Zaragoza 000099182 245__ $$aIndependent genomic polymorphisms in the PknH serine threonine kinase locus during evolution of the Mycobacterium tuberculosis Complex affect virulence and host preference 000099182 260__ $$c2020 000099182 5060_ $$aAccess copy available to the general public$$fUnrestricted 000099182 5203_ $$aSpecies belonging to the Mycobacterium tuberculosis Complex (MTBC) show more than 99% genetic identity but exhibit distinct host preference and virulence. The molecular genetic changes that underly host specificity and infection phenotype within MTBC members have not been fully elucidated. Here, we analysed RD900 genomic region across MTBC members using whole genome sequences from 60 different MTBC strains so as to determine its role in the context of MTBC evolutionary history. The RD900 region comprises two homologous genes, pknH1 and pknH2, encoding a serine/threonine protein kinase PknH flanking the tbd2 gene. Our analysis revealed that RD900 has been independently lost in different MTBC lineages and different strains, resulting in the generation of a single pknH gene. Importantly, all the analysed M. bovis and M. caprae strains carry a conserved deletion within a proline rich-region of pknH, independent of the presence or absence of RD900. We hypothesized that deletion of pknH proline rich-region in M. bovis may affect PknH function, having a potential role in its virulence and evolutionary adaptation. To explore this hypothesis, we constructed two M. bovis ‘knock-in’ strains containing the M. tuberculosis pknH gene. Evaluation of their virulence phenotype in mice revealed a reduced virulence of both M. bovis knock-in strains compared to the wild type, suggesting that PknH plays an important role in the differential virulence phenotype of M. bovis vs M. tuberculosis. 000099182 536__ $$9info:eu-repo/grantAgreement/ES/MCIU/RTI2018-097625-B-I00 000099182 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/ 000099182 590__ $$a6.823$$b2020 000099182 591__ $$aMICROBIOLOGY$$b20 / 136 = 0.147$$c2020$$dQ1$$eT1 000099182 591__ $$aVIROLOGY$$b7 / 36 = 0.194$$c2020$$dQ1$$eT1 000099182 591__ $$aPARASITOLOGY$$b3 / 38 = 0.079$$c2020$$dQ1$$eT1 000099182 592__ $$a3.718$$b2020 000099182 593__ $$aGenetics$$c2020$$dQ1 000099182 593__ $$aImmunology$$c2020$$dQ1 000099182 593__ $$aVirology$$c2020$$dQ1 000099182 593__ $$aMolecular Biology$$c2020$$dQ1 000099182 593__ $$aParasitology$$c2020$$dQ1 000099182 593__ $$aMicrobiology$$c2020$$dQ1 000099182 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion 000099182 700__ $$aFarrell, D. 000099182 700__ $$aMa, R. 000099182 700__ $$0(orcid)0000-0001-7866-2803$$aUranga, S.$$uUniversidad de Zaragoza 000099182 700__ $$0(orcid)0000-0002-9713-2127$$aGomez, A.B.$$uUniversidad de Zaragoza 000099182 700__ $$0(orcid)0000-0002-2787-9671$$aMonzon, M.$$uUniversidad de Zaragoza 000099182 700__ $$0(orcid)0000-0002-7173-7216$$aBadiola, J.$$uUniversidad de Zaragoza 000099182 700__ $$0(orcid)0000-0002-5175-8394$$aAnel, A.$$uUniversidad de Zaragoza 000099182 700__ $$0(orcid)0000-0001-8841-6593$$aGonzalo-Asensio, J.$$uUniversidad de Zaragoza 000099182 700__ $$0(orcid)0000-0003-2993-5478$$aMartin, C.$$uUniversidad de Zaragoza 000099182 700__ $$aGordon, S.V. 000099182 700__ $$0(orcid)0000-0001-7897-9173$$aAguilo, N.$$uUniversidad de Zaragoza 000099182 7102_ $$11011$$2630$$aUniversidad de Zaragoza$$bDpto. Microb.Ped.Radio.Sal.Pú.$$cÁrea Microbiología 000099182 7102_ $$11003$$2443$$aUniversidad de Zaragoza$$bDpto. Anatom.Histolog.Humanas$$cArea Histología 000099182 7102_ $$11009$$2773$$aUniversidad de Zaragoza$$bDpto. Patología Animal$$cÁrea Sanidad Animal 000099182 7102_ $$11011$$2X$$aUniversidad de Zaragoza$$bDpto. Microb.Ped.Radio.Sal.Pú.$$cProy. investigación HQA 000099182 7102_ $$11002$$2060$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Bioquímica y Biolog.Mole. 000099182 773__ $$g16, 12 (2020), e1009061[24 pp]$$pPLoS Pathog.$$tPLoS Pathogens$$x1553-7366 000099182 8564_ $$s756355$$uhttps://zaguan.unizar.es/record/99182/files/texto_completo.pdf$$yVersión publicada 000099182 8564_ $$s2401917$$uhttps://zaguan.unizar.es/record/99182/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada 000099182 909CO $$ooai:zaguan.unizar.es:99182$$particulos$$pdriver 000099182 951__ $$a2021-09-02-10:58:52 000099182 980__ $$aARTICLE