Dataset Information

Differential gene expression in Leishmania [SPP.] promastigotes. Leishmania chagasi

ABSTRACT: Leishmania chagasi is the causative agent of zoonotic visceral leishmaniasis in Brazil, being domestic and stray dogs the main reservoirs. The development of the parasite involves two stages. The promastigote is extracellular and develops within the sand fly gut. The amastigote survives inside the harsh environment of the phagolysosome of mammalian host phagocytes, where pH is acidic, temperature higher than in the sand fly vector and hydrolytic enzymes act. In addition, the host phagocyte displays the nitric oxide defense mechanism against the amastigote. Promastigotes are also able to withstand NO even when they develop within the sand fly gut. This can be explained with the pre-adaptative hypothesis, which has been supported by us and others elsewhere and consists of preparation of promastigotes in advance for development towards the amastigote stage. For this reason, the comparison of NO-resistant and sensitive promastigotes is valuable. The two-dimension electrophoresis-mass spectrometry (2DE-MS/MS) approach has been performed to study differential protein abundance comparing L. chagasi NO-sensitive and resistant promastigotes. This analysis has revealed differential expression of genes directly and indirectly involved in NO-resistance, highlighting up-regulation of the glucose-6-phosphate dehydrogenase (G6PD) in NO-resistant promastigotes and down-regulation of the glutathione peroxidase (GPX) and the arginase (ARG) in NO-sensitive ones. These data are a starting point in the search of vaccine candidates and/or drug targets.

INSTRUMENT(S): 4800 Proteomics Analyzer

ORGANISM(S): Leishmania Chagasi

SUBMITTER: J. Alberto Medina-Aunon

LAB HEAD: Vicente Larraga

PROVIDER: PXD002939 | Pride | 2016-03-31

REPOSITORIES: Pride

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Publications

Proteome profiling of the growth phases of Leishmania pifanoi promastigotes in axenic culture reveals differential abundance of immunostimulatory proteins.

Alcolea Pedro J PJ Alonso Ana A García-Tabares Francisco F Mena María Del Carmen MDC Ciordia Sergio S Larraga Vicente V

Acta tropica 20160315

Leishmaniasis is a term that encompasses a compendium of neglected tropical diseases caused by dimorphic and digenetic protozoan parasites from the genus Leishmania (Kinetoplastida: Trypanosomatidae). The clinical manifestations of neotropical cutaneous leishmaniasis (NCL) caused by Leishmania pifanoi and other species of the "Leishmania mexicana complex" mainly correspond to anergic diffuse cutaneous leishmaniasis (ADCL), which is the origin of considerable morbidity. Despite the outstanding ad ...[more]

PMID: 26992294

Similar Datasets

Project description:Protozoa of the genus Leishmania are the causative agents of leishmaniasis in humans. These parasites cycle between promastigotes in the sand fly mid-gut and amastigotes in phagolysosome of mammalian macrophages. During infection, host up-regulate nitric oxide synthase and parasite induce host arginase expression, both of which use arginine as a substrate. These elevated activities deplete macrophage arginine pools, a situation that invading Leishmania must overcome since it is an essential amino acid. Leishmania donovani imports exogenous arginine via a mono-specific amino acid transporter (AAP3) and utilizes it primarily through the polyamine pathway to provide precursors for trypanothione biosynthesis. Here we report the discovery of a pathway whereby promastigote and amastigote forms of the Leishmania sense the lack of environmental arginine and respond with rapid up-regulation in AAP3 expression and activity, as well as several other transporters. Significantly, this arginine deprivation response is also activated in parasites during macrophage infection. Phosphoproteomic analyses of L. donovani promastigotes have implicated a Mitogen-Activated Protein Kinase 2 (MPK2)-mediated signaling cascade in this response and L. mexicana mutants lacking MPK2 are unable to respond to arginine deprivation. In this study, we established that Leishmania cells sense the absence of arginine in their environment; both in culture (axenic promastigotes and amastigotes) and in macrophages during infection (amastigotes). This study describes the first amino acid deprivation sensing mechanism and the pathway that transduce this response, and reveals a novel host-pathogen metabolic interplay. Total RNA from Ten Leishmania donovani samples were analyzed using RNA-Seq. Cells from two life stages (promastigotes and amastigotes) were grown in axenic culture in the presence and absense of arginine. For each condition two biological replicates were grown and analyzed. In addition two macrophage grown amastigotes were analyzed.

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