000056091 001__ 56091
000056091 005__ 20210121114541.0
000056091 0247_ $$2doi$$a10.1128/mBio.01289-15
000056091 0248_ $$2sideral$$a92698
000056091 037__ $$aART-2015-92698
000056091 041__ $$aeng
000056091 100__ $$0(orcid)0000-0003-4155-749X$$aBroset, E.$$uUniversidad de Zaragoza
000056091 245__ $$aEvolutionary landscape of the mycobacterium tuberculosis complex from the viewpoint of phoPR: Implications for virulence regulation and application to vaccine development
000056091 260__ $$c2015
000056091 5060_ $$aAccess copy available to the general public$$fUnrestricted
000056091 5203_ $$aDifferent members of the Mycobacterium genus have evolved to cause tuberculosis in diverse human populations and in a variety of animal species. Our cumulative knowledge of mycobacterial genomes indicates that mutations in the PhoPR two-component virulence system were acquired not only during the natural evolution of mycobacterial species but also during in vitro subculture, which has given rise to the attenuated reference strain H37Ra or to different daughter strains of Mycobacterium bovis BCG. PhoPR is a well-known regulator of pathogenic phenotypes, including secretion of the virulence factor ESAT-6, biosynthesis of acyltrehalose-based lipids, and modulation of antigen export, in members of the Mycobacterium tuberculosis complex (MTBC)Evolutionarily conserved polymorphisms in PhoPR from Mycobacterium africanum, M. bovis, or M. tuberculosis H37Ra result in loss of functional phenotypes. Interestingly, some members of the MTBC have acquired compensatory mutations to counteract these polymorphisms and, probably, to maintain their pathogenic potential. Some of these compensatory mutations include the insertion of the IS6110 element upstream from phoPR in a particular M. bovis strain that is able to transmit between humans or polymorphisms in M. africanum and M. bovis that affect the regulatory region of the espACD operon, allowing PhoPR-independent ESAT-6 secretion. This review highlights the increasing knowledge of the significance of PhoPR in the evolution of the MTBC and its potential application in the construction of new attenuated vaccines based on phoPR inactivation. In this context, the live attenuated vaccine MTBVAC, based on a phoP fadD26 deletion mutant of M. tuberculosis, is the first vaccine of this kind to successfully enter into clinical development, representing a historic milestone in the field of human vaccinology.
000056091 536__ $$9info:eu-repo/grantAgreement/ES/MINECO/BIO2014-5258P$$9info:eu-repo/grantAgreement/ES/MINECO/BES-2012-052937$$9info:eu-repo/grantAgreement/ES/ISCIII/PI12-01970$$9This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No H2020 643381-TBVAC2020$$9info:eu-repo/grantAgreement/EC/H2020/643381/EU/TBVAC2020; Advancing novel and promising TB vaccine candidates from discovery to preclinical and early clinical development/TBVAC2020
000056091 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000056091 590__ $$a6.975$$b2015
000056091 591__ $$aMICROBIOLOGY$$b13 / 123 = 0.106$$c2015$$dQ1$$eT1
000056091 592__ $$a4.028$$b2015
000056091 593__ $$aVirology$$c2015$$dQ1
000056091 593__ $$aMicrobiology$$c2015$$dQ1
000056091 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000056091 700__ $$0(orcid)0000-0003-2993-5478$$aMartín, C.$$uUniversidad de Zaragoza
000056091 700__ $$0(orcid)0000-0001-8841-6593$$aGonzalo-Asensio, J.$$uUniversidad de Zaragoza
000056091 7102_ $$11008$$2630$$aUniversidad de Zaragoza$$bDpto. Microb.Med.Pr.,Sal.Públ.$$cÁrea Microbiología
000056091 773__ $$g6, 5 (2015), [10 pp]$$pMBIO$$tMBIO$$x2161-2129
000056091 8564_ $$s1396905$$uhttps://zaguan.unizar.es/record/56091/files/texto_completo.pdf$$yVersión publicada
000056091 8564_ $$s134798$$uhttps://zaguan.unizar.es/record/56091/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000056091 909CO $$ooai:zaguan.unizar.es:56091$$particulos$$pdriver
000056091 951__ $$a2021-01-21-11:16:32
000056091 980__ $$aARTICLE