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Abstract
Mycobacterium 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 [ver mas...]
dc.contributor.authorMondino, Sonia
dc.contributor.authorVazquez, Cristina Lourdes
dc.contributor.authorCabruja, Matias
dc.contributor.authorSala, Claudia
dc.contributor.authorCazenave-Gassiot, Amaury
dc.contributor.authorBlanco, Federico Carlos
dc.contributor.authorWenk, Markus R.
dc.contributor.authorBigi, Fabiana
dc.contributor.authorCole, Stewart T.
dc.contributor.authorGramajo, Hugo
dc.contributor.authorGago, Gabriela
dc.date.accessioned2021-02-18T11:05:31Z
dc.date.available2021-02-18T11:05:31Z
dc.date.issued2020-10
dc.identifier.issn1664-302X
dc.identifier.otherhttps://doi.org/10.3389/fmicb.2020.586285
dc.identifier.urihttp://hdl.handle.net/20.500.12123/8675
dc.identifier.urihttps://www.frontiersin.org/articles/10.3389/fmicb.2020.586285/full
dc.description.abstractMycobacterium 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.eng
dc.formatapplication/pdfes_AR
dc.language.isoenges_AR
dc.publisherFrontiers Mediaes_AR
dc.rightsinfo:eu-repo/semantics/openAccesses_AR
dc.sourceFrontiers in Microbiology 11 : 586285 (Octubre 2020)es_AR
dc.subjectTuberculosises_AR
dc.subjectBiosynthesiseng
dc.subjectBiosíntesises_AR
dc.subjectHomeostasises_AR
dc.subjectVirulenceeng
dc.subjectVirulenciaes_AR
dc.subjectMycobacterium tuberculosises_AR
dc.titleFasR regulates fatty acid biosynthesis and is essential for virulence of Mycobacterium tuberculosises_AR
dc.typeinfo:ar-repo/semantics/artículoes_AR
dc.typeinfo:eu-repo/semantics/articlees_AR
dc.typeinfo:eu-repo/semantics/publishedVersiones_AR
dc.description.origenInstituto de Biotecnologíaes_AR
dc.description.filFil: Mondino, Sonia. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario. Laboratory of Physiology and Genetics of Actinomycetes; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentinaes_AR
dc.description.filFil: Vazquez, Cristina Lourdes. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Biotecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentinaes_AR
dc.description.filFil: Cabruja, Matias. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario. Laboratory of Physiology and Genetics of Actinomycetes; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentinaes_AR
dc.description.filFil: Sala, Claudia. Ecole Polytechnique Fédérale de Lausanne. Global Health Institute; Suizaes_AR
dc.description.filFil: Cazenave-Gassiot, Amaury. National University of Singapore. Yong Loo Lin School of Medicine. Department of Biochemistry. Singapore Lipidomics Incubator; Singapures_AR
dc.description.filFil: Blanco, Federico Carlos. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Biotecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentinaes_AR
dc.description.filFil: Wenk, Markus R. National University of Singapore. Yong Loo Lin School of Medicine. Department of Biochemistry. Singapore Lipidomics Incubator; Singapures_AR
dc.description.filFil: Bigi, Fabiana. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Biotecnología; Argentina. Consejo Nacional de investigaciones Científicas y Tecnológicas; Argentinaes_AR
dc.description.filFil: Cole, Stewart T. Ecole Polytechnique Fédérale de Lausanne. Global Health Institute; Suizaes_AR
dc.description.filFil: Gramajo, Hugo. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario. Laboratory of Physiology and Genetics of Actinomycetes; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentinaes_AR
dc.description.filFil: Gago, Gabriela. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario. Laboratory of Physiology and Genetics of Actinomycetes; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentinaes_AR
dc.subtypecientifico


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