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


Autoria(s): Silva, Maria Fernanda Laranjeira da; Zampieri, Ricardo Andrade; Muxel, Sandra M.; Beverley, Stephen M.; Winter, Lucile Maria Floeter
Contribuinte(s)

UNIVERSIDADE DE SÃO PAULO

Data(s)

04/11/2013

04/11/2013

2012

Resumo

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 (arg Delta SKL) restored growth but failed to restore infectivity. Further study showed that the ARG Delta SKL 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.

Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)

Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)

Conselho Nacional para o Desenvolvimento Cientifico e Tecnologico (CNPq)

Conselho Nacional para o Desenvolvimento Cientifico e Tecnologico (CNPq)

National Institute of Health [AI 21903, AI 29646]

National Institute of Health

Identificador

PLOS ONE, SAN FRANCISCO, v. 7, n. 3, supl. 1, Part 2, pp. 336-365, 11018, 2012

1932-6203

http://www.producao.usp.br/handle/BDPI/37983

10.1371/journal.pone.0034022

http://dx.doi.org/10.1371/journal.pone.0034022

Idioma(s)

eng

Publicador

PUBLIC LIBRARY SCIENCE

SAN FRANCISCO

Relação

PLOS ONE

Direitos

openAccess

Copyright PUBLIC LIBRARY SCIENCE

Palavras-Chave #L-ARGININE #TRYPANOSOMA-BRUCEI #GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE #MURINE MACROPHAGES #METABOLISM #ENZYMES #BIOSYNTHESIS #AMASTIGOTES #PREDICTION #GROWTH #MULTIDISCIPLINARY SCIENCES
Tipo

article

original article

publishedVersion