000127090 001__ 127090
000127090 005__ 20241125101143.0
000127090 0247_ $$2doi$$a10.1371/journal.ppat.1011437
000127090 0248_ $$2sideral$$a134505
000127090 037__ $$aART-2023-134505
000127090 041__ $$aeng
000127090 100__ $$aMalaga, Wladimir
000127090 245__ $$aNatural mutations in the sensor kinase of the PhoPR two-component regulatory system modulate virulence of ancestor-like tuberculosis bacilli
000127090 260__ $$c2023
000127090 5060_ $$aAccess copy available to the general public$$fUnrestricted
000127090 5203_ $$aThe molecular factors and genetic adaptations that contributed to the emergence of Mycobacterium tuberculosis (MTB) from an environmental Mycobacterium canettii-like ancestor, remain poorly investigated. In MTB, the PhoPR two-component regulatory system controls production and secretion of proteins and lipid virulence effectors. Here, we describe that several mutations, present in phoR of M. canettii relative to MTB, impact the expression of the PhoP regulon and the pathogenicity of the strains. First, we establish a molecular model of PhoR and show that some substitutions found in PhoR of M. canettii are likely to impact the structure and activity of this protein. Second, we show that STB-K, the most attenuated available M. canettii strain, displays lower expression of PhoP-induced genes than MTB. Third, we demonstrate that genetic swapping of the phoPR allele from STB-K with the ortholog from MTB H37Rv enhances expression of PhoP-controlled functions and the capacities of the recombinant strain to colonize human macrophages, the MTB target cells, as well as to cause disease in several mouse infection models. Fourth, we extended these observations to other M. canettii strains and confirm that PhoP-controlled functions are expressed at lower levels in most M. canettii strains than in M. tuberculosis. Our findings suggest that distinct PhoR variants have been selected during the evolution of tuberculosis bacilli, contributing to higher pathogenicity and persistence of MTB in the mammalian host.
000127090 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000127090 590__ $$a5.5$$b2023
000127090 592__ $$a2.223$$b2023
000127090 591__ $$aMICROBIOLOGY$$b24 / 161 = 0.149$$c2023$$dQ1$$eT1
000127090 593__ $$aGenetics$$c2023$$dQ1
000127090 591__ $$aVIROLOGY$$b6 / 41 = 0.146$$c2023$$dQ1$$eT1
000127090 593__ $$aImmunology$$c2023$$dQ1
000127090 591__ $$aPARASITOLOGY$$b3 / 45 = 0.067$$c2023$$dQ1$$eT1
000127090 593__ $$aVirology$$c2023$$dQ1
000127090 593__ $$aMolecular Biology$$c2023$$dQ1
000127090 593__ $$aParasitology$$c2023$$dQ1
000127090 593__ $$aMicrobiology$$c2023$$dQ1
000127090 594__ $$a11.4$$b2023
000127090 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000127090 700__ $$aPayros, Delphine
000127090 700__ $$aMeunier, Eva
000127090 700__ $$aFrigui, Wafa
000127090 700__ $$aSayes, Fadel
000127090 700__ $$aPawlik, Alexandre
000127090 700__ $$aOrgeur, Mickael
000127090 700__ $$aBerrone, Céline
000127090 700__ $$aMoreau, Flavie
000127090 700__ $$aMazères, Serge
000127090 700__ $$0(orcid)0000-0001-8841-6593$$aGonzalo-Asensio, Jesus$$uUniversidad de Zaragoza
000127090 700__ $$aRengel, David
000127090 700__ $$0(orcid)0000-0003-2993-5478$$aMartin, Carlos$$uUniversidad de Zaragoza
000127090 700__ $$aAstarie-Dequeker, Catherine
000127090 700__ $$aMourey, Lionel
000127090 700__ $$aBrosch, Roland
000127090 700__ $$aGuilhot, Christophe
000127090 7102_ $$11011$$2630$$aUniversidad de Zaragoza$$bDpto. Microb.Ped.Radio.Sal.Pú.$$cÁrea Microbiología
000127090 773__ $$g19, 7 (2023), e1011437 [25 pp]$$pPLoS Pathog.$$tPLoS Pathogens$$x1553-7366
000127090 8564_ $$s2982647$$uhttps://zaguan.unizar.es/record/127090/files/texto_completo.pdf$$yVersión publicada
000127090 8564_ $$s2445074$$uhttps://zaguan.unizar.es/record/127090/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000127090 909CO $$ooai:zaguan.unizar.es:127090$$particulos$$pdriver
000127090 951__ $$a2024-11-22-12:03:29
000127090 980__ $$aARTICLE