Intracellular Mycobacterium leprae Utilizes Host Glucose as a Carbon Source in Schwann Cells

Detalhes bibliográficos
Autor(a) principal: Borah, Khushboo
Data de Publicação: 2019
Outros Autores: Girardi, Karina do Carmo de Vasconcelos, Mendum, Tom A., Lery, Leticia Miranda Santos, Beste, Dany J. V., Lara, Flavio Alves, Pessolani, Maria Cristina Vidal, McFadden, Johnjoe
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/40995
Resumo: University of Surrey. Faculty of Health and Medical Sciences. Guildford, United Kingdom.
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spelling Borah, KhushbooGirardi, Karina do Carmo de VasconcelosMendum, Tom A.Lery, Leticia Miranda SantosBeste, Dany J. V.Lara, Flavio AlvesPessolani, Maria Cristina VidalMcFadden, Johnjoe2020-04-27T17:58:06Z2020-04-27T17:58:06Z2019BORAH, Khushboo et al. Intracellular Mycobacterium leprae Utilizes Host Glucose as a Carbon Source in Schwann Cells. mBio, v. 10, n. 6, p. 1-9, Nov./Dec. 2019.2150-7511https://www.arca.fiocruz.br/handle/icict/4099510.1128/mBio.02351-19engAmerican Society for MicrobiologyMycobacterium lepraeCélulas de SchwannGlicoseMycobacterium tuberculosisMacrófagoFosfoenolpiruvato carboxilaseMetabolismo do carbonoMycobacterium lepraeSchwann cellsGlucoseMycobacterium tuberculosisMacrophagePhosphoenolpyruvate carboxylaseCarbon metabolismIntracellular Mycobacterium leprae Utilizes Host Glucose as a Carbon Source in Schwann Cellsinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleUniversity of Surrey. Faculty of Health and Medical Sciences. Guildford, United Kingdom.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Microbiologia Celular. Rio de Janeiro, RJ, Brasil.University of Surrey. Faculty of Health and Medical Sciences. Guildford, United Kingdom.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Microbiologia Celular. Rio de Janeiro, RJ, Brasil.University of Surrey. Faculty of Health and Medical Sciences. Guildford, United Kingdom.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Microbiologia Celular. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Microbiologia Celular. Rio de Janeiro, RJ, Brasil.University of Surrey. Faculty of Health and Medical Sciences. Guildford, United Kingdom.New approaches are needed to control leprosy, but understanding of the biology of the causative agent Mycobacterium leprae remains rudimentary, principally because the pathogen cannot be grown in axenic culture. Here, we applied 13C isotopomer analysis to measure carbon metabolism of M. leprae in its primary host cell, the Schwann cell. We compared the results of this analysis with those of a related pathogen, Mycobacterium tuberculosis, growing in its primary host cell, the macrophage. Using 13C isotopomer analysis with glucose as the tracer, we show that whereas M. tuberculosis imports most of its amino acids directly from the host macrophage, M. leprae utilizes host glucose pools as the carbon source to biosynthesize the majority of its amino acids. Our analysis highlights the anaplerotic enzyme phosphoenolpyruvate carboxylase required for this intracellular diet of M. leprae, identifying this enzyme as a potential antileprosy drug target.IMPORTANCE Leprosy remains a major problem in the world today, particularly affecting the poorest and most disadvantaged sections of society in the least developed countries of the world. The long-term aim of research is to develop new treatments and vaccines, and these aims are currently hampered by our inability to grow the pathogen in axenic culture. In this study, we probed the metabolism of M. leprae while it is surviving and replicating inside its primary host cell, the Schwann cell, and compared it to a related pathogen, M. tuberculosis, replicating in macrophages. Our analysis revealed that unlike M. tuberculosis, M. leprae utilized host glucose as a carbon source and that it biosynthesized its own amino acids, rather than importing them from its host cell. We demonstrated that the enzyme phosphoenolpyruvate carboxylase plays a crucial role in glucose catabolism in M. leprae Our findings provide the first metabolic signature of M. leprae in the host Schwann cell and identify novel avenues for the development of antileprosy drugs.info:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-82991https://www.arca.fiocruz.br/bitstream/icict/40995/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALFlavioLara_MCVIdalPessolani_etal_IOC_2019.pdfFlavioLara_MCVIdalPessolani_etal_IOC_2019.pdfapplication/pdf1130648https://www.arca.fiocruz.br/bitstream/icict/40995/2/FlavioLara_MCVIdalPessolani_etal_IOC_2019.pdfe6ae520b51b717f185c51ded2a22dcfaMD52TEXTFlavioLara_MCVIdalPessolani_etal_IOC_2019.pdf.txtFlavioLara_MCVIdalPessolani_etal_IOC_2019.pdf.txtExtracted 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dc.title.pt_BR.fl_str_mv Intracellular Mycobacterium leprae Utilizes Host Glucose as a Carbon Source in Schwann Cells
title Intracellular Mycobacterium leprae Utilizes Host Glucose as a Carbon Source in Schwann Cells
spellingShingle Intracellular Mycobacterium leprae Utilizes Host Glucose as a Carbon Source in Schwann Cells
Borah, Khushboo
Mycobacterium leprae
Células de Schwann
Glicose
Mycobacterium tuberculosis
Macrófago
Fosfoenolpiruvato carboxilase
Metabolismo do carbono
Mycobacterium leprae
Schwann cells
Glucose
Mycobacterium tuberculosis
Macrophage
Phosphoenolpyruvate carboxylase
Carbon metabolism
title_short Intracellular Mycobacterium leprae Utilizes Host Glucose as a Carbon Source in Schwann Cells
title_full Intracellular Mycobacterium leprae Utilizes Host Glucose as a Carbon Source in Schwann Cells
title_fullStr Intracellular Mycobacterium leprae Utilizes Host Glucose as a Carbon Source in Schwann Cells
title_full_unstemmed Intracellular Mycobacterium leprae Utilizes Host Glucose as a Carbon Source in Schwann Cells
title_sort Intracellular Mycobacterium leprae Utilizes Host Glucose as a Carbon Source in Schwann Cells
author Borah, Khushboo
author_facet Borah, Khushboo
Girardi, Karina do Carmo de Vasconcelos
Mendum, Tom A.
Lery, Leticia Miranda Santos
Beste, Dany J. V.
Lara, Flavio Alves
Pessolani, Maria Cristina Vidal
McFadden, Johnjoe
author_role author
author2 Girardi, Karina do Carmo de Vasconcelos
Mendum, Tom A.
Lery, Leticia Miranda Santos
Beste, Dany J. V.
Lara, Flavio Alves
Pessolani, Maria Cristina Vidal
McFadden, Johnjoe
author2_role author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Borah, Khushboo
Girardi, Karina do Carmo de Vasconcelos
Mendum, Tom A.
Lery, Leticia Miranda Santos
Beste, Dany J. V.
Lara, Flavio Alves
Pessolani, Maria Cristina Vidal
McFadden, Johnjoe
dc.subject.other.pt_BR.fl_str_mv Mycobacterium leprae
Células de Schwann
Glicose
Mycobacterium tuberculosis
Macrófago
Fosfoenolpiruvato carboxilase
Metabolismo do carbono
topic Mycobacterium leprae
Células de Schwann
Glicose
Mycobacterium tuberculosis
Macrófago
Fosfoenolpiruvato carboxilase
Metabolismo do carbono
Mycobacterium leprae
Schwann cells
Glucose
Mycobacterium tuberculosis
Macrophage
Phosphoenolpyruvate carboxylase
Carbon metabolism
dc.subject.en.pt_BR.fl_str_mv Mycobacterium leprae
Schwann cells
Glucose
Mycobacterium tuberculosis
Macrophage
Phosphoenolpyruvate carboxylase
Carbon metabolism
description University of Surrey. Faculty of Health and Medical Sciences. Guildford, United Kingdom.
publishDate 2019
dc.date.issued.fl_str_mv 2019
dc.date.accessioned.fl_str_mv 2020-04-27T17:58:06Z
dc.date.available.fl_str_mv 2020-04-27T17:58:06Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.citation.fl_str_mv BORAH, Khushboo et al. Intracellular Mycobacterium leprae Utilizes Host Glucose as a Carbon Source in Schwann Cells. mBio, v. 10, n. 6, p. 1-9, Nov./Dec. 2019.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/40995
dc.identifier.issn.pt_BR.fl_str_mv 2150-7511
dc.identifier.doi.none.fl_str_mv 10.1128/mBio.02351-19
identifier_str_mv BORAH, Khushboo et al. Intracellular Mycobacterium leprae Utilizes Host Glucose as a Carbon Source in Schwann Cells. mBio, v. 10, n. 6, p. 1-9, Nov./Dec. 2019.
2150-7511
10.1128/mBio.02351-19
url https://www.arca.fiocruz.br/handle/icict/40995
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv American Society for Microbiology
publisher.none.fl_str_mv American Society for Microbiology
dc.source.none.fl_str_mv reponame:Repositório Institucional da FIOCRUZ (ARCA)
instname:Fundação Oswaldo Cruz (FIOCRUZ)
instacron:FIOCRUZ
instname_str Fundação Oswaldo Cruz (FIOCRUZ)
instacron_str FIOCRUZ
institution FIOCRUZ
reponame_str Repositório Institucional da FIOCRUZ (ARCA)
collection Repositório Institucional da FIOCRUZ (ARCA)
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