000061484 001__ 61484
000061484 005__ 20190529115217.0
000061484 0247_ $$2doi$$a10.1371/journal.ppat.1004183
000061484 0248_ $$2sideral$$a89449
000061484 037__ $$aART-2014-89449
000061484 041__ $$aeng
000061484 100__ $$0(orcid)0000-0003-0865-9339$$aSolans, L.
000061484 245__ $$aThe PhoP-Dependent ncRNA Mcr7 Modulates the TAT Secretion System in Mycobacterium tuberculosis
000061484 260__ $$c2014
000061484 5060_ $$aAccess copy available to the general public$$fUnrestricted
000061484 5203_ $$aThe PhoPR two-component system is essential for virulence in Mycobacterium tuberculosis where it controls expression of approximately 2% of the genes, including those for the ESX-1 secretion apparatus, a major virulence determinant. Mutations in phoP lead to compromised production of pathogen-specific cell wall components and attenuation both ex vivo and in vivo. Using antibodies against the native protein in ChIP-seq experiments (chromatin immunoprecipitation followed by high-throughput sequencing) we demonstrated that PhoP binds to at least 35 loci on the M. tuberculosis genome. The PhoP regulon comprises several transcriptional regulators as well as genes for polyketide synthases and PE/PPE proteins. Integration of ChIP-seq results with high-resolution transcriptomic analysis (RNA-seq) revealed that PhoP controls 30 genes directly, whilst regulatory cascades are responsible for signal amplification and downstream effects through proteins like EspR, which controls Esx1 function, via regulation of the espACD operon. The most prominent site of PhoP regulation was located in the intergenic region between rv2395 and PE_PGRS41, where the mcr7 gene codes for a small non-coding RNA (ncRNA). Northern blot experiments confirmed the absence of Mcr7 in an M. tuberculosis phoP mutant as well as low-level expression of the ncRNA in M. tuberculosis complex members other than M. tuberculosis. By means of genetic and proteomic analyses we demonstrated that Mcr7 modulates translation of the tatC mRNA thereby impacting the activity of the Twin Arginine Translocation (Tat) protein secretion apparatus. As a result, secretion of the immunodominant Ag85 complex and the beta-lactamase BlaC is affected, among others. Mcr7, the first ncRNA of M. tuberculosis whose function has been established, therefore represents a missing link between the PhoPR two-component system and the downstream functions necessary for successful infection of the host.
000061484 536__ $$9info:eu-repo/grantAgreement/ES/MINECO/BIO2011-23555$$9info:eu-repo/grantAgreement/ES/MINECO/BES-2009-013037$$9info:eu-repo/grantAgreement/ES/MICINN/Juan de la Cierva Program-JCI-2009-03799$$9info:eu-repo/grantAgreement/EC/FP7/241745/EU/Discovery and preclinical development of new generation tuberculosis vaccines/NEWTBVAC
000061484 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000061484 590__ $$a7.562$$b2014
000061484 591__ $$aMICROBIOLOGY$$b10 / 119 = 0.084$$c2014$$dQ1$$eT1
000061484 591__ $$aVIROLOGY$$b2 / 33 = 0.061$$c2014$$dQ1$$eT1
000061484 591__ $$aPARASITOLOGY$$b2 / 36 = 0.056$$c2014$$dQ1$$eT1
000061484 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000061484 700__ $$0(orcid)0000-0001-8841-6593$$aGonzalo-Asensio, J.$$uUniversidad de Zaragoza
000061484 700__ $$aSala, C.
000061484 700__ $$aBenjak, A.
000061484 700__ $$aUplekar, S.
000061484 700__ $$aRougemont, J.
000061484 700__ $$aGuilhot, C.
000061484 700__ $$aMalaga, W.
000061484 700__ $$0(orcid)0000-0003-2993-5478$$aMartín, C.$$uUniversidad de Zaragoza
000061484 700__ $$aCole, S.T.
000061484 7102_ $$11008$$2630$$aUniversidad de Zaragoza$$bDpto. Microb.Med.Pr.,Sal.Públ.$$cÁrea Microbiología
000061484 773__ $$g10, 5 (2014), e1004183 [17pp]$$pPLoS Pathog.$$tPLoS Pathogens$$x1553-7366
000061484 8564_ $$s2679253$$uhttp://zaguan.unizar.es/record/61484/files/texto_completo.pdf$$yVersión publicada
000061484 8564_ $$s130062$$uhttp://zaguan.unizar.es/record/61484/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000061484 909CO $$ooai:zaguan.unizar.es:61484$$particulos$$pdriver
000061484 951__ $$a2019-05-29-11:40:50
000061484 980__ $$aARTICLE