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Leishmania amazonensis Arginase Compartmentalization in the Glycosome Is Important for Parasite Infectivity

In Leishmania, de novo polyamine synthesis is initiated by the cleavage of L-arginine to urea and L-ornithine by the action of arginase (ARG, E.C. 3.5.3.1). Previous studies in L. major and L. mexicana showed that ARG is essential for in vitro growth in the absence of polyamines and needed for full...

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Autores principales: da Silva, Maria Fernanda Laranjeira, Zampieri, Ricardo Andrade, Muxel, Sandra M., Beverley, Stephen M., Floeter-Winter, Lucile M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3316525/
https://www.ncbi.nlm.nih.gov/pubmed/22479507
http://dx.doi.org/10.1371/journal.pone.0034022
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author da Silva, Maria Fernanda Laranjeira
Zampieri, Ricardo Andrade
Muxel, Sandra M.
Beverley, Stephen M.
Floeter-Winter, Lucile M.
author_facet da Silva, Maria Fernanda Laranjeira
Zampieri, Ricardo Andrade
Muxel, Sandra M.
Beverley, Stephen M.
Floeter-Winter, Lucile M.
author_sort da Silva, Maria Fernanda Laranjeira
collection PubMed
description In Leishmania, de novo polyamine synthesis is initiated by the cleavage of L-arginine to urea and L-ornithine by the action of arginase (ARG, E.C. 3.5.3.1). Previous studies in L. major and L. mexicana showed that ARG is essential for in vitro growth in the absence of polyamines and needed for full infectivity in animal infections. The ARG protein is normally found within the parasite glycosome, and here we examined whether this localization is required for survival and infectivity. First, the localization of L. amazonensis ARG in the glycosome was confirmed in both the promastigote and amastigote stages. As in other species, arg(−) L. amazonensis required putrescine for growth and presented an attenuated infectivity. Restoration of a wild type ARG to the arg (−) mutant restored ARG expression, growth and infectivity. In contrast, restoration of a cytosol-targeted ARG lacking the glycosomal SKL targeting sequence (argΔSKL) restored growth but failed to restore infectivity. Further study showed that the ARGΔSKL protein was found in the cytosol as expected, but at very low levels. Our results indicate that the proper compartmentalization of L. amazonensis arginase in the glycosome is important for enzyme activity and optimal infectivity. Our conjecture is that parasite arginase participates in a complex equilibrium that defines the fate of L-arginine and that its proper subcellular location may be essential for this physiological orchestration.
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spelling pubmed-33165252012-04-04 Leishmania amazonensis Arginase Compartmentalization in the Glycosome Is Important for Parasite Infectivity da Silva, Maria Fernanda Laranjeira Zampieri, Ricardo Andrade Muxel, Sandra M. Beverley, Stephen M. Floeter-Winter, Lucile M. PLoS One Research Article In Leishmania, de novo polyamine synthesis is initiated by the cleavage of L-arginine to urea and L-ornithine by the action of arginase (ARG, E.C. 3.5.3.1). Previous studies in L. major and L. mexicana showed that ARG is essential for in vitro growth in the absence of polyamines and needed for full infectivity in animal infections. The ARG protein is normally found within the parasite glycosome, and here we examined whether this localization is required for survival and infectivity. First, the localization of L. amazonensis ARG in the glycosome was confirmed in both the promastigote and amastigote stages. As in other species, arg(−) L. amazonensis required putrescine for growth and presented an attenuated infectivity. Restoration of a wild type ARG to the arg (−) mutant restored ARG expression, growth and infectivity. In contrast, restoration of a cytosol-targeted ARG lacking the glycosomal SKL targeting sequence (argΔSKL) restored growth but failed to restore infectivity. Further study showed that the ARGΔSKL protein was found in the cytosol as expected, but at very low levels. Our results indicate that the proper compartmentalization of L. amazonensis arginase in the glycosome is important for enzyme activity and optimal infectivity. Our conjecture is that parasite arginase participates in a complex equilibrium that defines the fate of L-arginine and that its proper subcellular location may be essential for this physiological orchestration. Public Library of Science 2012-03-30 /pmc/articles/PMC3316525/ /pubmed/22479507 http://dx.doi.org/10.1371/journal.pone.0034022 Text en da Silva et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
da Silva, Maria Fernanda Laranjeira
Zampieri, Ricardo Andrade
Muxel, Sandra M.
Beverley, Stephen M.
Floeter-Winter, Lucile M.
Leishmania amazonensis Arginase Compartmentalization in the Glycosome Is Important for Parasite Infectivity
title Leishmania amazonensis Arginase Compartmentalization in the Glycosome Is Important for Parasite Infectivity
title_full Leishmania amazonensis Arginase Compartmentalization in the Glycosome Is Important for Parasite Infectivity
title_fullStr Leishmania amazonensis Arginase Compartmentalization in the Glycosome Is Important for Parasite Infectivity
title_full_unstemmed Leishmania amazonensis Arginase Compartmentalization in the Glycosome Is Important for Parasite Infectivity
title_short Leishmania amazonensis Arginase Compartmentalization in the Glycosome Is Important for Parasite Infectivity
title_sort leishmania amazonensis arginase compartmentalization in the glycosome is important for parasite infectivity
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3316525/
https://www.ncbi.nlm.nih.gov/pubmed/22479507
http://dx.doi.org/10.1371/journal.pone.0034022
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