Intracellular Mycobacterium leprae Utilizes Host Glucose as a Carbon Source in Schwann Cells
Autor(a) principal: | |
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Data de Publicação: | 2019 |
Outros Autores: | , , , , , , |
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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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 |
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FIOCRUZ |
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FIOCRUZ |
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Repositório Institucional da FIOCRUZ (ARCA) |
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Repositório Institucional da FIOCRUZ (ARCA) |
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