LFR1 Ferric Iron Reductase of Leishmania amazonensis Is Essential for the Generation of Infective Parasite Forms
Autor(a) principal: | |
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Data de Publicação: | 2011 |
Outros Autores: | , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNIFESP |
Texto Completo: | http://repositorio.unifesp.br/handle/11600/33822 http://dx.doi.org/10.1074/jbc.M111.229674 |
Resumo: | The protozoan parasite Leishmania is the causative agent of serious human infections worldwide. the parasites alternate between insect and vertebrate hosts and cause disease by invading macrophages, where they replicate. Parasites lacking the ferrous iron transporter LIT1 cannot grow intracellularly, indicating that a plasma membrane-associated mechanism for iron uptake is essential for the establishment of infections. Here, we identify and functionally characterize a second member of the Leishmania iron acquisition pathway, the ferric iron reductase LFR1. the LFR1 gene is up-regulated under iron deprivation and accounts for all the detectable ferric reductase activity exposed on the surface of Leishmania amazonensis. LFR1 null mutants grow normally as promastigote insect stages but are defective in differentiation into the vertebrate infective forms, metacyclic promastigotes and amastigotes. LFR1 overexpression partially restores the abnormal morphology of infective stages but markedly reduces parasite viability, precluding its ability to rescue LFR1 null replication in macrophages. However, LFR1 overexpression is not toxic for amastigotes lacking the ferrous iron transporter LIT1 and rescues their growth defect. in addition, the intracellular growth of both LFR1 and LIT1 null parasites is rescued in macrophages loaded with exogenous iron. This indicates that the Fe(3+) reductase LFR1 functions upstream of LIT1 and suggests that LFR1 overexpression results in excessive Fe(2+) production, which impairs parasite viability after intracellular transport by LIT1. |
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Flannery, Andrew R.Huynh, ChauMittra, BidyottamMortara, Renato A. [UNIFESP]Andrews, Norma W.Univ MarylandUniversidade Federal de São Paulo (UNIFESP)2016-01-24T14:16:55Z2016-01-24T14:16:55Z2011-07-01Journal of Biological Chemistry. Bethesda: Amer Soc Biochemistry Molecular Biology Inc, v. 286, n. 26, p. 23266-23279, 2011.0021-9258http://repositorio.unifesp.br/handle/11600/33822http://dx.doi.org/10.1074/jbc.M111.22967410.1074/jbc.M111.229674WOS:000292025000060The protozoan parasite Leishmania is the causative agent of serious human infections worldwide. the parasites alternate between insect and vertebrate hosts and cause disease by invading macrophages, where they replicate. Parasites lacking the ferrous iron transporter LIT1 cannot grow intracellularly, indicating that a plasma membrane-associated mechanism for iron uptake is essential for the establishment of infections. Here, we identify and functionally characterize a second member of the Leishmania iron acquisition pathway, the ferric iron reductase LFR1. the LFR1 gene is up-regulated under iron deprivation and accounts for all the detectable ferric reductase activity exposed on the surface of Leishmania amazonensis. LFR1 null mutants grow normally as promastigote insect stages but are defective in differentiation into the vertebrate infective forms, metacyclic promastigotes and amastigotes. LFR1 overexpression partially restores the abnormal morphology of infective stages but markedly reduces parasite viability, precluding its ability to rescue LFR1 null replication in macrophages. However, LFR1 overexpression is not toxic for amastigotes lacking the ferrous iron transporter LIT1 and rescues their growth defect. in addition, the intracellular growth of both LFR1 and LIT1 null parasites is rescued in macrophages loaded with exogenous iron. This indicates that the Fe(3+) reductase LFR1 functions upstream of LIT1 and suggests that LFR1 overexpression results in excessive Fe(2+) production, which impairs parasite viability after intracellular transport by LIT1.National Institutes of HealthUniv Maryland, Dept Cell Biol & Mol Genet, College Pk, MD 20742 USAUniversidade Federal de São Paulo, Dept Microbiol Immunol & Parasitol, BR-04023062 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Microbiol Immunol & Parasitol, BR-04023062 São Paulo, BrazilNational Institutes of Health: R01 AI067979Web of Science23266-23279engAmer Soc Biochemistry Molecular Biology IncJournal of Biological ChemistryLFR1 Ferric Iron Reductase of Leishmania amazonensis Is Essential for the Generation of Infective Parasite Formsinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESP11600/338222022-09-27 09:48:30.82metadata only accessoai:repositorio.unifesp.br:11600/33822Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestopendoar:34652022-09-27T12:48:30Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false |
dc.title.en.fl_str_mv |
LFR1 Ferric Iron Reductase of Leishmania amazonensis Is Essential for the Generation of Infective Parasite Forms |
title |
LFR1 Ferric Iron Reductase of Leishmania amazonensis Is Essential for the Generation of Infective Parasite Forms |
spellingShingle |
LFR1 Ferric Iron Reductase of Leishmania amazonensis Is Essential for the Generation of Infective Parasite Forms Flannery, Andrew R. |
title_short |
LFR1 Ferric Iron Reductase of Leishmania amazonensis Is Essential for the Generation of Infective Parasite Forms |
title_full |
LFR1 Ferric Iron Reductase of Leishmania amazonensis Is Essential for the Generation of Infective Parasite Forms |
title_fullStr |
LFR1 Ferric Iron Reductase of Leishmania amazonensis Is Essential for the Generation of Infective Parasite Forms |
title_full_unstemmed |
LFR1 Ferric Iron Reductase of Leishmania amazonensis Is Essential for the Generation of Infective Parasite Forms |
title_sort |
LFR1 Ferric Iron Reductase of Leishmania amazonensis Is Essential for the Generation of Infective Parasite Forms |
author |
Flannery, Andrew R. |
author_facet |
Flannery, Andrew R. Huynh, Chau Mittra, Bidyottam Mortara, Renato A. [UNIFESP] Andrews, Norma W. |
author_role |
author |
author2 |
Huynh, Chau Mittra, Bidyottam Mortara, Renato A. [UNIFESP] Andrews, Norma W. |
author2_role |
author author author author |
dc.contributor.institution.none.fl_str_mv |
Univ Maryland Universidade Federal de São Paulo (UNIFESP) |
dc.contributor.author.fl_str_mv |
Flannery, Andrew R. Huynh, Chau Mittra, Bidyottam Mortara, Renato A. [UNIFESP] Andrews, Norma W. |
description |
The protozoan parasite Leishmania is the causative agent of serious human infections worldwide. the parasites alternate between insect and vertebrate hosts and cause disease by invading macrophages, where they replicate. Parasites lacking the ferrous iron transporter LIT1 cannot grow intracellularly, indicating that a plasma membrane-associated mechanism for iron uptake is essential for the establishment of infections. Here, we identify and functionally characterize a second member of the Leishmania iron acquisition pathway, the ferric iron reductase LFR1. the LFR1 gene is up-regulated under iron deprivation and accounts for all the detectable ferric reductase activity exposed on the surface of Leishmania amazonensis. LFR1 null mutants grow normally as promastigote insect stages but are defective in differentiation into the vertebrate infective forms, metacyclic promastigotes and amastigotes. LFR1 overexpression partially restores the abnormal morphology of infective stages but markedly reduces parasite viability, precluding its ability to rescue LFR1 null replication in macrophages. However, LFR1 overexpression is not toxic for amastigotes lacking the ferrous iron transporter LIT1 and rescues their growth defect. in addition, the intracellular growth of both LFR1 and LIT1 null parasites is rescued in macrophages loaded with exogenous iron. This indicates that the Fe(3+) reductase LFR1 functions upstream of LIT1 and suggests that LFR1 overexpression results in excessive Fe(2+) production, which impairs parasite viability after intracellular transport by LIT1. |
publishDate |
2011 |
dc.date.issued.fl_str_mv |
2011-07-01 |
dc.date.accessioned.fl_str_mv |
2016-01-24T14:16:55Z |
dc.date.available.fl_str_mv |
2016-01-24T14:16:55Z |
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 |
Journal of Biological Chemistry. Bethesda: Amer Soc Biochemistry Molecular Biology Inc, v. 286, n. 26, p. 23266-23279, 2011. |
dc.identifier.uri.fl_str_mv |
http://repositorio.unifesp.br/handle/11600/33822 http://dx.doi.org/10.1074/jbc.M111.229674 |
dc.identifier.issn.none.fl_str_mv |
0021-9258 |
dc.identifier.doi.none.fl_str_mv |
10.1074/jbc.M111.229674 |
dc.identifier.wos.none.fl_str_mv |
WOS:000292025000060 |
identifier_str_mv |
Journal of Biological Chemistry. Bethesda: Amer Soc Biochemistry Molecular Biology Inc, v. 286, n. 26, p. 23266-23279, 2011. 0021-9258 10.1074/jbc.M111.229674 WOS:000292025000060 |
url |
http://repositorio.unifesp.br/handle/11600/33822 http://dx.doi.org/10.1074/jbc.M111.229674 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.ispartof.none.fl_str_mv |
Journal of Biological Chemistry |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
23266-23279 |
dc.publisher.none.fl_str_mv |
Amer Soc Biochemistry Molecular Biology Inc |
publisher.none.fl_str_mv |
Amer Soc Biochemistry Molecular Biology Inc |
dc.source.none.fl_str_mv |
reponame:Repositório Institucional da UNIFESP instname:Universidade Federal de São Paulo (UNIFESP) instacron:UNIFESP |
instname_str |
Universidade Federal de São Paulo (UNIFESP) |
instacron_str |
UNIFESP |
institution |
UNIFESP |
reponame_str |
Repositório Institucional da UNIFESP |
collection |
Repositório Institucional da UNIFESP |
repository.name.fl_str_mv |
Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP) |
repository.mail.fl_str_mv |
|
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1802764163537174528 |