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dc.contributor.authorMartinot, Amanda Jezeken_US
dc.date.accessioned2015-03-18T13:09:15Z
dash.embargo.terms2017-03-01en_US
dc.date.created2015-03en_US
dc.date.issued2015-01-23en_US
dc.date.submitted2015en_US
dc.identifier.citationMartinot, Amanda Jezek. 2015. Mycobacterial Metabolic Syndrome: Triglyceride Accumulation Decreases Growth Rate and Virulence of Mycobacterium Tuberculosis. Doctoral dissertation, Harvard University, Graduate School of Arts & Sciences.en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:14226055
dc.description.abstractMycobacterium tuberculosis (Mtb) mutants lacking the operon Rv1411c-1410c encoding a lipoprotein, Rv1411c (LprG) and a putative transporter, Rv1410c (Rv1410) are dramatically attenuated for growth in mice. Previous work in our lab, using the model organism Mycobacterium smegmatis, suggested that this operon regulated the lipid content of the cell wall. Work in other laboratories characterizing LprG as a lipid-binding lipoprotein lead us to hypothesize that these bacteria grew poorly due to loss of a key lipid important in the host-pathogen interaction. Based on structural and biochemical studies we hypothesized that this attenuation was due to a lipid transport defect. Using whole cell lipidomic analysis, we found changes in LprG-1410 mutants including accumulation of triacylglyceride (TAG) species in the absence of the transport system. We have identified TAG in outer membrane fractions and supernatants of Mtb, have demonstrated the ability of LprG to transport TAG in an in vitro vesicle transfer assay, and have co-crystallized LprG with TAG. Moreover, accumulation of intracellular TAG substantially decreases growth under carbon stress in vitro and in vivo in the mouse model. Our results suggest a far different model – that TAG is ordinarily transported out of the cell and, in the absence of a transporter, limits cell proliferation independent of the host immune response. This suggests that TAG is a key metabolic regulator of cellular growth within the host.en_US
dc.format.mimetypeapplication/pdfen_US
dc.language.isoenen_US
dash.licenseLAAen_US
dc.subjectBiology, Microbiologyen_US
dc.subjectBiology, Geneticsen_US
dc.titleMycobacterial Metabolic Syndrome: Triglyceride Accumulation Decreases Growth Rate and Virulence of Mycobacterium Tuberculosisen_US
dc.typeThesis or Dissertationen_US
dash.depositing.authorMartinot, Amanda Jezeken_US
dc.date.available2017-03-01T08:31:18Z
thesis.degree.date2015en_US
thesis.degree.grantorGraduate School of Arts & Sciencesen_US
thesis.degree.levelDoctoralen_US
thesis.degree.nameDoctor of Philosophyen_US
dc.contributor.committeeMemberMitchell, Jamesen_US
dc.contributor.committeeMemberLee, Tun-Houen_US
dc.contributor.committeeMemberSassetti, Chrisen_US
dc.type.materialtexten_US
thesis.degree.departmentBiological Sciences in Public Healthen_US
dash.identifier.vireohttp://etds.lib.harvard.edu/gsas/admin/view/122en_US
dc.description.keywordsTB; Mtb; triglyceride; triacylglycerol;triacylglyceride; virulence; mouse; carbon; lipidomics; lipiden_US
dash.author.emailamandamartinot@gmail.comen_US
dash.identifier.drsurn-3:HUL.DRS.OBJECT:25119225en_US
dash.identifier.orcid0000-0001-6237-6191en_US
dash.contributor.affiliatedMartinot, Amanda
dc.identifier.orcid0000-0001-6237-6191


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