• JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
 
  Bookmark and Share
 
 
Doctoral Thesis
DOI
Document
Author
Full name
Mauricio Scavassini Penã
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2018
Supervisor
Committee
Carboni, Beatriz Simonsen Stolf (President)
Miguel, Danilo Ciccone
Negro, Sonia Jancar
Tosi, Luiz Ricardo Orsini
Wunderlich, Gerhard
Title in Portuguese
Estudo dos efeitos da proteína LaLRR17 de Leishmania (L.) amazonensis na infecção do macrófago e identificação de seus possíveis ligantes.
Keywords in Portuguese
Leishmania amazonensis
Phage Display GRP78
LaLRR17
Abstract in Portuguese
Leishmania spp. são protozoários parasitas transmitidos a vertebrados pela picada de insetos flebotomíneos fêmeas. Apresentam duas formas principais em seu ciclo de vida: promastigotas e amastigotas. Os promastigotas vivem no intestino do hospedeiro invertebrado. Os amastigotas vivem preferencialmente no interior de macrófagos, fagócitos profissionais capazes de destruir patógenos. Para isso, são capazes de burlar a atividade microbicida desses macrófagos, sobreviver e se multiplicar em seu interior. Essa capacidade se deve a diversas moléculas produzidas pelo parasita, denominadas fatores de virulência, que ajudam em sua internalizarão e proliferação na célula hospedeira. A proteína LaLRR17 de Leishmania (L.) amazonensis recebeu esse nome porque contém em sua região central seis repetições ricas em leucina (LRRs) e por seu gene se localizar no cromossomo 17. Os motivos LRR de diversos organismos estão normalmente envolvidos em interações proteicas. A LaLRR17 é expressa em promastigotas e amastigotas, e foi detectada no citoplasma do macrófago infectado. Parasitas superexpressores dessa proteína apresentaram aumento da infectividade in vitro. Acreditamos que a proteína LaLRR17 participa de interações com moléculas de macrófagos, e que essas interações estão associadas à virulência dessa proteína. No entanto, não eram conhecidas moléculas do macrófago interagiam com a LaLRR17. O Phage Display é uma técnica baseada na expressão de proteínas sintéticas nos capsídeos de fagos que tem sido utilizada para identificação de ligantes de proteínas. A aplicação do Phage Display sobre a LaLRR17 recombinante permitiu identificar potenciais ligantes dessa proteína no macrófago, e aliada a cromatografia de afinidade, apontou diversos candidatos que podem participar do aumento de virulência conferido pela LaLRR17, entre eles o mais promissor, GRP78 do macrófago, que tem papel efetivo na fagocitose da Leishmania mediada pela LaLRR17.
Title in English
Effects of LaLRR17 protein from Leishmania (L.) amazonensis in macrophage infection and identification of its possible ligands.
Keywords in English
Leishmania amazonensis
Phage Display GRP78
LaLRR17
Abstract in English
Leishmania spp. are protozoan parasites transmitted to vertebrates by the bite of female phlebotomine insects. They present two main forms in their life cycle: promastigotes and amastigotes. Promastigotes live in the gut of the invertebrate host. The amastigotes live preferably in macrophages, "professional phagocytes" capable of destroying pathogens. They are able to circumvent the microbicidal activity of macrophages, survive and multiply inside them. This ability is due to several molecules produced by the parasite, called virulence factors, which help their internalization and proliferation inside the host cell. The protein LaLRR17 of L. (L) amazonensis was named because contains in its central region six leucine-rich repeats (LRRs) and its gene locates on chromosome 17. LRR motifs of various organisms are usually involved in protein-protein interactions. LaLRR17 is expressed in promastigotes and amastigotes, and was detected in the cytoplasm of the infected macrophage. Parasites overexpressing this protein showed increased infectivity in vitro. We believe that LaLRR17 participates in interactions with macrophages molecules, and that these interactions are associated with the virulence this protein. However, we do not know which molecules from the macrophage interact with LaLRR17. Phage Display is a technique based on the expression of synthetic proteins in phage capsids that has been used to identify protein binders. The application of Phage Display on recombinant LaLRR17 allowed the identification of potential ligands of this protein in the macrophage, and allied to affinity chromatography, pointed out several candidates that could participate in the increased virulence conferred by LaLRR17, among them the most promising macrophage GRP78, which plays an effective role in LaLRR17-mediated Leishmania phagocytosis.
 
WARNING - Viewing this document is conditioned on your acceptance of the following terms of use:
This document is only for private use for research and teaching activities. Reproduction for commercial use is forbidden. This rights cover the whole data about this document as well as its contents. Any uses or copies of this document in whole or in part must include the author's name.
Release Date
2021-04-17
Publishing Date
2019-05-06
 
WARNING: Learn what derived works are clicking here.
All rights of the thesis/dissertation are from the authors
CeTI-SC/STI
Digital Library of Theses and Dissertations of USP. Copyright © 2001-2020. All rights reserved.