FasR regulates fatty acid biosynthesis and is essential for virulence of Mycobacterium tuberculosis

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dc.audiencePara citar este articulo: Mondino S, Vázquez CL, Cabruja M, Sala C, Cazenave-Gassiot A, Blanco FC, Wenk MR, Bigi F, Cole ST, Gramajo H and Gago G (2020) FasR Regulates Fatty Acid Biosynthesis and Is Essential for Virulence of Mycobacterium tuberculosis. Front. Microbiol. 11:586285. doi: 10.3389/fmicb.2020.586285
dc.citation.titleFrontiers in Microbiologyes
dc.citation.volume11es
dc.creatorMondino, Sonia Soledad
dc.creatorVázquez, Cristina L.
dc.creatorCabruja, Matías Ezequiel
dc.creatorSala, Claudia
dc.creatorCazenave-Gassiot, Amaury
dc.creatorBlanco, Federico C.
dc.creatorWenk, Markus R.
dc.creatorBigi, Fabiana
dc.creatorCole, Stewart T.
dc.creatorGramajo, Hugo Cesar
dc.creatorGago, Gabriela
dc.date.accessioned2021-04-20T22:23:56Z
dc.date.available2021-04-20T22:23:56Z
dc.date.issued2020-10-27
dc.descriptionMycobacterium tuberculosis, the etiologic agent of human tuberculosis, is the world’s leading cause of death from an infectious disease. One of the main features of this pathogen is the complex and dynamic lipid composition of the cell envelope, which adapts to the variable host environment and defines the fate of infection by actively interacting with and modulating immune responses. However, while much has been learned about the enzymes of the numerous lipid pathways, little knowledge is available regarding the proteins and metabolic signals regulating lipid metabolism during M. tuberculosis infection. In this work, we constructed and characterized a FasR-deficient mutant in M. tuberculosis and demonstrated that FasR positively regulates fas and acpS expression. Lipidomic analysis of the wild type and mutant strains revealed complete rearrangement of most lipid components of the cell envelope, with phospholipids, mycolic acids, sulfolipids, and phthiocerol dimycocerosates relative abundance severely altered. As a consequence, replication of the mutant strain was impaired in macrophages leading to reduced virulence in a mouse model of infection. Moreover, we show that the fasR mutant resides in acidified cellular compartments, suggesting that the lipid perturbation caused by the mutation prevented M. tuberculosis inhibition of phagolysosome maturation. This study identified FasR as a novel factor involved in regulation of mycobacterial virulence and provides evidence for the essential role that modulation of lipid homeostasis plays in the outcome of M. tuberculosis infection.es
dc.description.filFil: Mondino, Sonia Soledad. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario (IBR -CONICET). Laboratorio de Fisiología y Genética de Actinomycetes; Argentina.es
dc.description.filFil: Vázquez, Cristina L. Instituto Nacional de Tecnología Agropecuaria (INTA) - Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET). Instituto de Agrobiotecnología y Biología Molecular (IABIMO); Argentinaes
dc.description.filFil: Cabruja, Matías Ezequiel. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario (IBR -CONICET). Laboratorio de Fisiología y Genética de Actinomycetes; Argentina.es
dc.description.filFil: Sala, Claudia. Ecole Polytechnique Fédérale de Lausanne. Global Health Institute; Switzerland.es
dc.description.filFil: Cazenave-Gassiot, Amaury. National University of Singapore. Yong Loo Lin School of Medicine. Department of Biochemistry. Singapore Lipidomics Incubator (SLING); Singapore.es
dc.description.filFil: Blanco, Federico C. Instituto Nacional de Tecnología Agropecuaria (INTA) - Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET). Instituto de Agrobiotecnología y Biología Molecular (IABIMO); Argentinaes
dc.description.filFil: Wenk, Markus R. National University of Singapore. Yong Loo Lin School of Medicine. Department of Biochemistry. Singapore Lipidomics Incubator (SLING); Singapore.es
dc.description.filFil: Bigi, Fabiana. Instituto Nacional de Tecnología Agropecuaria (INTA) - Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET). Instituto de Agrobiotecnología y Biología Molecular (IABIMO); Argentinaes
dc.description.filFil: Cole, Stewart T. Ecole Polytechnique Fédérale de Lausanne. Global Health Institute; Switzerland.es
dc.description.filFil: Gramajo, Hugo Cesar. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario (IBR -CONICET). Laboratorio de Fisiología y Genética de Actinomycetes; Argentina.es
dc.description.filFil: Gago, Gabriela. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario (IBR -CONICET). Laboratorio de Fisiología y Genética de Actinomycetes; Argentina.es
dc.description.sponsorshipAgencia Nacional de Promoción Científica y Tecnológica (ANPCyT): 2015-0796, 2018-02539 y 2015–2022es
dc.description.sponsorshipNational Institutes of Health (NIH): 1R01AI095183-01es
dc.formatapplication/pdf
dc.formatapplication/pdf
dc.format.extent1-12es
dc.identifier.issn1664-302Xes
dc.identifier.urihttp://hdl.handle.net/2133/20529
dc.language.isoenges
dc.publisherFrontiers Mediaes
dc.relation.publisherversionhttps://doi.org/10.3389/fmicb.2020.586285es
dc.relation.publisherversionhttps://www.frontiersin.org/articles/10.3389/fmicb.2020.586285/fulles
dc.rightsopenAccesses
dc.rights.holderUniversidad Nacional de Rosarioes
dc.rights.holderMondino, Sonia Soledades
dc.rights.holderVázquez, Cristina L.es
dc.rights.holderCabruja, Matías Ezequieles
dc.rights.holderSala, Claudiaes
dc.rights.holderCazenave-Gassiot, Amauryes
dc.rights.holderBlanco, Federico C.es
dc.rights.holderWenk, Markus R.es
dc.rights.holderBigi, Fabianaes
dc.rights.holderCole, Stewart T.es
dc.rights.holderGramajo, Hugo Cesares
dc.rights.holderGago, Gabrielaes
dc.rights.textAttribution 4.0 International (CC BY 4.0)es
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/*
dc.subjectTuberculosises
dc.subjectFatty Acid Biosynthesises
dc.subjectLipid Homeostasises
dc.subjectMycobacteriaes
dc.subjectVirulencees
dc.subjectMycobacterial Cell Envelopees
dc.titleFasR regulates fatty acid biosynthesis and is essential for virulence of Mycobacterium tuberculosises
dc.typearticle
dc.typeartículo
dc.typepublishedVersion
dc.type.collectionarticulo
dc.type.versionpublishedVersiones

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