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Published on: July 31, 2019
Cell surface proteome analysis of human-hosted Trypanosoma cruzi life stages
Rayner M L Queiroz1, Sébastien Charneau, Izabela M D Bastos
1Department of Cell Biology, Institute of Biology, University of Brasilia , Brasília, Brazil.
Insights
Researchers analyzed the plasma membrane proteins of Trypanosoma cruzi, the parasite causing Chagas
Area of Science:
- Parasitology
- Molecular Biology
- Biochemistry
Background:
- Chagas' disease, caused by Trypanosoma cruzi, is a significant neglected tropical disease.
- Current treatments for chronic Chagas' disease are limited, and no vaccine is available.
Purpose of the Study:
- To analyze the plasma membrane (PM) subproteome of Trypanosoma cruzi in its human-hosted life stages.
- To identify potential drug targets and understand parasite-host interactions.
Main Methods:
- Utilized two complementary PM protein enrichment techniques.
- Identified proteins using liquid chromatography-tandem mass spectrometry (LC-MS/MS).
- Performed bioinformatic analysis of identified proteins.
Main Results:
- Revealed an extensive repertoire of proteins in the PM subproteomes of trypomastigote and axenic amastigote stages.
- Identified stage-specific and shared enzymes, including potential drug targets.
- Bioinformatic analysis confirmed proteins are membrane-associated and involved in host cell infection, adhesion, signaling, and immune modulation.
Conclusions:
- The study identified numerous potential drug targets within the T. cruzi plasma membrane proteome.
- Understanding these proteins offers insights into parasite virulence and host-parasite interactions.
- Findings contribute to developing novel strategies against Chagas' disease.
Abstract:
Chagas' disease is a neglected infectious illness, caused by the protozoan Trypanosoma cruzi. It remains a challenging health issue in Latin America, where it is endemic, and so far there is no immunoprophylatic vaccine or satisfactory chemotherapic treatment for its chronic stage. The present work addressed the analysis of the plasma membrane (PM) subproteome from T. cruzi human-hosted life stages, trypomastigote and axenic amastigote, by two complementary PM protein enrichment techniques followed by identification using an LC-MS/MS approach. The results revealed an extensive repertoire of proteins in the PM subproteomes, including enzymes that might be suitable candidates for drug intervention. The comparison of the cell surface proteome among the life forms revealed some potentially stage-specific enzymes, although the majority was shared by both stages. Bioinformatic analysis showed that the vast majority of the identified proteins are membrane-derived and/or possess predicted transmembrane domains. They are mainly involved in host cell infection, protein adhesion, cell signaling, and the modulation of mammalian host immune response. Several virulence factors and proteins potentially capable of acting at a number of metabolic pathways of the host and also to regulate cell differentiation of the parasite itself were also found.
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