The essential role of cholesterol metabolism in the intracellular survival of Mycobacterium 2 leprae is not coupled to central carbon metabolism and energy production

Marques, Maria Angela M.; Pinho, Marcia Berrêdo; Rosa, Thabatta L. S. A.; Pujari, Venugopal; Lemes, Robertha M. R.; Lery, Leticia M. S.; Silva, Carlos Adriano M.; Guimarães, Ana Carolina R.; Atella, Georgia C.; Wheat, William H.; Brennam, Patrick J.; Crick, Dean D.; Belisle, John T.; Pessolani, Maria Cristina V.

The essential role of cholesterol metabolism in the intracellular survival of Mycobacterium 2 leprae is not coupled to central carbon metabolism and energy production

Detalhes bibliográficos
Autor(a) principal:	Marques, Maria Angela M.
Data de Publicação:	2015
Outros Autores:	Pinho, Marcia Berrêdo, Rosa, Thabatta L. S. A., Pujari, Venugopal, Lemes, Robertha M. R., Lery, Leticia M. S., Silva, Carlos Adriano M., Guimarães, Ana Carolina R., Atella, Georgia C., Wheat, William H., Brennam, Patrick J., Crick, Dean D., Belisle, John T., Pessolani, Maria Cristina V.
Tipo de documento:	Artigo
Idioma:	eng
Título da fonte:	Repositório Institucional da FIOCRUZ (ARCA)
DOI:	10.1128/JB.00625-15
Texto Completo:	https://www.arca.fiocruz.br/handle/icict/14319
Resumo:	Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Microbiologia Celular. Rio de Janeiro, RJ, Brasil / Colorado State University. Department of Microbiology, Immunology and Pathology. Fort Collins, CO, USA.

Metadados do item

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spelling	Marques, Maria Angela M.Pinho, Marcia BerrêdoRosa, Thabatta L. S. A.Pujari, VenugopalLemes, Robertha M. R.Lery, Leticia M. S.Silva, Carlos Adriano M.Guimarães, Ana Carolina R.Atella, Georgia C.Wheat, William H.Brennam, Patrick J.Crick, Dean D.Belisle, John T.Pessolani, Maria Cristina V.2016-05-17T16:50:23Z2016-05-17T16:50:23Z2015MARQUES, Maria Angela M. et al. The essential role of cholesterol metabolism in the intracellular survival of Mycobacterium leprae is not coupled to central carbon metabolism and energy production. J. Bacteriol.,v.197, n.23, p.3698-3707. Dec. 2015.0021-9193https://www.arca.fiocruz.br/handle/icict/1431910.1128/JB.00625-151098-5530engAmerican Society for MicrobiologyMycobacterium lepraeColesterolInfecçãoHanseníaseEstruturas celularesMycobacterium lepraeCholesterolInfectionLeprosyThe essential role of cholesterol metabolism in the intracellular survival of Mycobacterium 2 leprae is not coupled to central carbon metabolism and energy productioninfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Microbiologia Celular. Rio de Janeiro, RJ, Brasil / Colorado State University. Department of Microbiology, Immunology and Pathology. Fort Collins, CO, USA.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, BrasilColorado State University. Department of Microbiology, Immunology and Pathology. Fort Collins, CO, USAFundação Oswaldo Cruz.de Microbiologia Celular. Rio de Janeiro, RJ, Brasil Instituto Oswaldo Cruz. LaboratórioFundação Oswaldo Cruz.de Microbiologia Celular. Rio de Janeiro, RJ, Brasil Instituto Oswaldo Cruz. LaboratórioColorado State University. Department of Microbiology, Immunology and Pathology. Fort Collins, CO, USAFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Genômica Funcional e Bioinformática. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Bioquímica Médica. Laboratório de Bioquímica de Lipídeos e Lipoproteínas. Rio de Janeiro, RJ, Brasil.Colorado State University. Department of Microbiology, Immunology and Pathology. Fort Collins, CO, USAColorado State University. Department of Microbiology, Immunology and Pathology. Fort Collins, CO, USAColorado State University. Department of Microbiology, Immunology and Pathology. Fort Collins, CO, USAColorado State University. Department of Microbiology, Immunology and Pathology. Fort Collins, CO, USAFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Microbiologia Celular. Rio de Janeiro, RJ, Brasil.Mycobacterium leprae induces the formation of lipid droplets, which are recruited to pathogen-containing phagosomes in infected macrophages and Schwann cells. Cholesterol is among the lipids with increased abundance in M. leprae-infected cells, and intracellular survival relies on cholesterol accumulation. The present study investigated the capacity of M. leprae to acquire and metabolize cholesterol. In silico analyses showed that oxidation of cholesterol to cholest-4-en-3-one (cholestenone), the first step of cholesterol degradation catalyzed by the enzyme 3β-hydroxysteroid dehydrogenase (3β-HSD), is apparently the only portion of the cholesterol catabolic pathway seen in Mycobacterium tuberculosis preserved by M. leprae. Incubation of bacteria with radiolabeled cholesterol confirmed the in silico predictions. Radiorespirometry and lipid analyses performed after incubating M. leprae with [4-(14)C]cholesterol or [26-(14)C]cholesterol showed the inability of this pathogen to metabolize the sterol rings or the side chain of cholesterol as a source of energy and carbon. However, the bacteria avidly incorporated cholesterol and, as expected, converted it to cholestenone both in vitro and in vivo. Our data indicate that M. leprae has lost the capacity to degrade and utilize cholesterol as a nutritional source but retains the enzyme responsible for its oxidation to cholestenone. Thus, the essential role of cholesterol metabolism in the intracellular survival of M. leprae is uncoupled from central carbon metabolism and energy production. Further elucidation of cholesterol metabolism in the host cell during M. leprae infection will establish the mechanism by which this lipid supports M. leprae intracellular survival and will open new avenues for novel leprosy therapies. Our study focused on the obligate intracellular pathogen Mycobacterium leprae and its capacity to metabolize cholesterol. The data make an important contribution for those interested in understanding the mechanisms of mycobacterial pathogenesis, since they indicate that the essential role of cholesterol for M. leprae intracellular survival does not rely on its utilization as a nutritional source. Our findings reinforce the complexity of cholesterol's role in sustaining M. leprae infection. Further elucidation of cholesterol metabolism in the host cell during M. leprae infection will establish the mechanism by which this lipid supports M. leprae intracellular survival and will open new avenues for novel leprosy therapies.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/14319/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALve_mariaangela_marques_etal_IOC_2015.pdfve_mariaangela_marques_etal_IOC_2015.pdfapplication/pdf1927406https://www.arca.fiocruz.br/bitstream/icict/14319/5/ve_mariaangela_marques_etal_IOC_2015.pdf6e7006a12ff5b4742f91dade5890d0e4MD55mariaangela_marques_etal_IOC_2015.pdfmariaangela_marques_etal_IOC_2015.pdfVersão 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dc.title.pt_BR.fl_str_mv	The essential role of cholesterol metabolism in the intracellular survival of Mycobacterium 2 leprae is not coupled to central carbon metabolism and energy production
title	The essential role of cholesterol metabolism in the intracellular survival of Mycobacterium 2 leprae is not coupled to central carbon metabolism and energy production
spellingShingle	The essential role of cholesterol metabolism in the intracellular survival of Mycobacterium 2 leprae is not coupled to central carbon metabolism and energy production Marques, Maria Angela M. Mycobacterium leprae Colesterol Infecção Hanseníase Estruturas celulares Mycobacterium leprae Cholesterol Infection Leprosy
title_short	The essential role of cholesterol metabolism in the intracellular survival of Mycobacterium 2 leprae is not coupled to central carbon metabolism and energy production
title_full	The essential role of cholesterol metabolism in the intracellular survival of Mycobacterium 2 leprae is not coupled to central carbon metabolism and energy production
title_fullStr	The essential role of cholesterol metabolism in the intracellular survival of Mycobacterium 2 leprae is not coupled to central carbon metabolism and energy production
title_full_unstemmed	The essential role of cholesterol metabolism in the intracellular survival of Mycobacterium 2 leprae is not coupled to central carbon metabolism and energy production
title_sort	The essential role of cholesterol metabolism in the intracellular survival of Mycobacterium 2 leprae is not coupled to central carbon metabolism and energy production
author	Marques, Maria Angela M.
author_facet	Marques, Maria Angela M. Pinho, Marcia Berrêdo Rosa, Thabatta L. S. A. Pujari, Venugopal Lemes, Robertha M. R. Lery, Leticia M. S. Silva, Carlos Adriano M. Guimarães, Ana Carolina R. Atella, Georgia C. Wheat, William H. Brennam, Patrick J. Crick, Dean D. Belisle, John T. Pessolani, Maria Cristina V.
author_role	author
author2	Pinho, Marcia Berrêdo Rosa, Thabatta L. S. A. Pujari, Venugopal Lemes, Robertha M. R. Lery, Leticia M. S. Silva, Carlos Adriano M. Guimarães, Ana Carolina R. Atella, Georgia C. Wheat, William H. Brennam, Patrick J. Crick, Dean D. Belisle, John T. Pessolani, Maria Cristina V.
author2_role	author author author author author author author author author author author author author
dc.contributor.author.fl_str_mv	Marques, Maria Angela M. Pinho, Marcia Berrêdo Rosa, Thabatta L. S. A. Pujari, Venugopal Lemes, Robertha M. R. Lery, Leticia M. S. Silva, Carlos Adriano M. Guimarães, Ana Carolina R. Atella, Georgia C. Wheat, William H. Brennam, Patrick J. Crick, Dean D. Belisle, John T. Pessolani, Maria Cristina V.
dc.subject.other.pt_BR.fl_str_mv	Mycobacterium leprae Colesterol Infecção Hanseníase Estruturas celulares
topic	Mycobacterium leprae Colesterol Infecção Hanseníase Estruturas celulares Mycobacterium leprae Cholesterol Infection Leprosy
dc.subject.en.pt_BR.fl_str_mv	Mycobacterium leprae Cholesterol Infection Leprosy
description	Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Microbiologia Celular. Rio de Janeiro, RJ, Brasil / Colorado State University. Department of Microbiology, Immunology and Pathology. Fort Collins, CO, USA.
publishDate	2015
dc.date.issued.fl_str_mv	2015
dc.date.accessioned.fl_str_mv	2016-05-17T16:50:23Z
dc.date.available.fl_str_mv	2016-05-17T16:50:23Z
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	MARQUES, Maria Angela M. et al. The essential role of cholesterol metabolism in the intracellular survival of Mycobacterium leprae is not coupled to central carbon metabolism and energy production. J. Bacteriol.,v.197, n.23, p.3698-3707. Dec. 2015.
dc.identifier.uri.fl_str_mv	https://www.arca.fiocruz.br/handle/icict/14319
dc.identifier.issn.none.fl_str_mv	0021-9193
dc.identifier.doi.none.fl_str_mv	10.1128/JB.00625-15
dc.identifier.eissn.none.fl_str_mv	1098-5530
identifier_str_mv	MARQUES, Maria Angela M. et al. The essential role of cholesterol metabolism in the intracellular survival of Mycobacterium leprae is not coupled to central carbon metabolism and energy production. J. Bacteriol.,v.197, n.23, p.3698-3707. Dec. 2015. 0021-9193 10.1128/JB.00625-15 1098-5530
url	https://www.arca.fiocruz.br/handle/icict/14319
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)
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institution	FIOCRUZ
reponame_str	Repositório Institucional da FIOCRUZ (ARCA)
collection	Repositório Institucional da FIOCRUZ (ARCA)
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The essential role of cholesterol metabolism in the intracellular survival of Mycobacterium 2 leprae is not coupled to central carbon metabolism and energy production

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