Role of cTXNPx and OPB in virulence and drug resistance in Leishmania L. amazonensis and search for new virulence factors by comparative proteomics

• Grant number: 14/26777-4
• Support Opportunities: Regular Research Grants
• Start date: April 01, 2016
• End date: September 30, 2018
• Field of knowledge: Biological Sciences - Parasitology - Protozoology of Parasites
• Principal Investigator: Beatriz Simonsen Stolf
• Grantee: Beatriz Simonsen Stolf
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• City of the host institution: São Paulo

Abstract

Leishmania ssp. are protozoan parasites responsible for a complex of diseases known as leishmaniasis. The parasite has two main forms: promastigote flagellated in the insect digestive tract, and amastigote inside macrophages of the vertebrate host. Survival and multiplication inside these macrophages are guaranteed by evasion mechanisms based on parasite virulence factors. Proteome analysis is an efficient tool for identification of these factors. A previous study of our lab compared the proteomes of L. (L.) amazonensis amastigotes obtained from BALB/c and BALB/c nude lesions to analyze the impact of host T cell dependent response in parasite protein expression. Isoforms of Oligopeptidase B (OPB) and cytoplasmic Tryparedoxin peroxidase (cTXNPx), known virulence factors in trypanosomatids, were differentially expressed. In this project we intend to analyze the roles of OPB and cTXNPx in L. (L.) amazonensis virulence employing parasites overexpressing the proteins in murine models of in vitro and in vivo infection, and evaluating the resistance to oxidative stress of parasites overexpressing cTXNPx. We have recently observed that PH8 and LV79 strains of L. (L.) amazonensis cultivated in our lab show different virulence in C57BL/6 and BALB/c mice and in macrophages in vitro. While lesions by LV79 are smaller in both mouse lineages, significantly larger and earlier lesions are generated by PH8 strain. Accordingly, higher percentages of infected cells and amastigotes per cell are observed in in vitro infections with PH8 than LV79. We thus aim to compare the proteomes of these two parasite strains to identify potential virulence factors of L. (L.) amazonensis. We will also analyze if the strains differ in terms of phagocytosis by macrophages and induction of cytokines and NO by these cells. (AU)

Scientific publications

(The scientific publications listed on this page originate from the Web of Science or SciELO databases. Their authors have cited FAPESP grant or fellowship project numbers awarded to Principal Investigators or Fellowship Recipients, whether or not they are among the authors. This information is collected automatically and retrieved directly from those bibliometric databases.)

CAPELLI-PEIXOTO, JANAINA; MULE, SIMON NGAO; TANO, FABIA TOMIE; PALMISANO, GIUSEPPE; STOLF, BEATRIZ SIMONSEN. Proteomics and Leishmaniasis: Potential Clinical Applications. PROTEOMICS CLINICAL APPLICATIONS, v. 13, n. 6, AUG 2019. (17/26197-6, 17/04287-3, 14/26777-4, 14/06863-3, 18/18257-1, 18/15549-1, 17/04032-5)

PENA, MAURICIO S.; TANG, FENNY HUI FEN; FRANCO, FERNANDO ALVES DE LIMA; RODRIGUES, ALESSANDRO TAUNAY; CARRARA, GUILHERME MOREIRA PAIVA; ARAUJO, THAIS LARISSA SILVA; GIORDANO, RICARDO JOSE; PALMISANO, GIUSEPPE; DE CAMARGO, MARISTELA MARTINS; ULIANA, SILVIA RENI BORTOLIN; et al. Leishmania (L.) amazonensis LaLRR17 increases parasite entry in macrophage by a mechanism dependent on GRP78. Parasitology, v. 150, n. 10, p. 12-pg., 2023-09-01. (14/26777-4, 12/19135-0, 18/14972-8)

DE REZENDE, ELOIZA; KAWAHARA, REBECA; PENA, MAURICIO S.; PALMISANO, GIUSEPPE; STOLF, BEATRIZ S.. Quantitative proteomic analysis of amastigotes from Leishmania (L.) amazonensis LV79 and PH8 strains reveals molecular traits associated with the virulence phenotype. PLoS Neglected Tropical Diseases, v. 11, n. 11, NOV 2017. (14/26777-4)