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Analysis of the participation of Oligopeptidase B and Cytoplasmic Tryparedoxin Peroxidase in virulence of Leishmania (Leishmania) amazonensis.

Grant number: 13/13527-7
Support type:Scholarships in Brazil - Master
Effective date (Start): September 01, 2013
Effective date (End): September 30, 2015
Field of knowledge:Biological Sciences - Parasitology - Protozoology of Parasites
Principal researcher:Beatriz Simonsen Stolf
Grantee:Karoline Mathias Leite
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated scholarship(s):14/16399-2 - Enzymatic characterization of tryparedoxin cytoplasmic peroxidase of Leishmania (L.) amazonensis and effect of overexpression in resistance to oxidative stress and protein expression of the parasite, BE.EP.MS

Abstract

Leishmania ssp. parasitic protozoa are responsible for a disease complex known as leishmaniasis. Present two major developmental forms: a flagellated promastigotes in the digestive all of the vector, and without flagella external amastigotes, within cells of the mononuclear phagocyte system, preferably macrophages vertebrate host. The ability for survival and multiplication in specialized cells in the destruction of pathogens due to the ability of the parasite to evade the microbicidal property of these cells for the production of molecules called virulence factors. Previous studies from our laboratory compared the proteome of amastigotes of L. (L) amazonensis lesions obtained from BALB / c and BALB / c nude in order to analyze the impact of the presence of T lymphocytes in the expression of proteins of the parasite. Among the differentially expressed proteins found to oligopeptidase B (OPB), a serine peptidase that hydrolyzes peptides up to 30 amino acid residues lysine and arginine, and cytoplasmic tryparedoxin peroxidase (cTXNPx), antioxidant protein that participates in the detoxification of hydroperoxides. Both were significantly expressed in the absence of T-lymphocytes, that is, in parasites isolated from BALB / c nude and have been described as virulence factors in trypanosomes. In fact, promastigotes of L. (L.) major deficient OPB showed significant reduction in infection and survival in macrophages in vitro and injuries to slower evolution in the murine model of infection in the leg. Similarly, promastigotes of L. (L.) donovani superexpressoras of cTXNPx had higher parasite load in macrophages in vitro. Considering this information and the importance of L. (L.) amazonensis in the epidemiology of leishmaniasis in Brazil, our objective is to analyze the importance of OPB and cTXNPx in virulence of this species using murine models of infection in vitro and in vivo.

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