Reprogramming of Trypanosoma cruzi metabolism triggered by parasite interaction with the host cell extracellular matrix.
Trypanosoma cruzi, the etiological agent of Chagas' disease, affects 8 million people predominantly living in socioeconomic underdeveloped areas. T. cruzi trypomastigotes (Ty), the classical infective stage, interact with the extracellular matrix (ECM), an obligatory step before invasion of alm...
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ftdoajarticles:oai:doaj.org/article:9a2d59abface415f985f6452e9286cf4 2023-05-15T15:13:17+02:00 Reprogramming of Trypanosoma cruzi metabolism triggered by parasite interaction with the host cell extracellular matrix. Eliciane C Mattos Gisele Canuto Nubia C Manchola Rubens D M Magalhães Thomas W M Crozier Douglas J Lamont Marina F M Tavares Walter Colli Michael A J Ferguson Maria Júlia M Alves 2019-02-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0007103 https://doaj.org/article/9a2d59abface415f985f6452e9286cf4 EN eng Public Library of Science (PLoS) https://doi.org/10.1371/journal.pntd.0007103 https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0007103 https://doaj.org/article/9a2d59abface415f985f6452e9286cf4 PLoS Neglected Tropical Diseases, Vol 13, Iss 2, p e0007103 (2019) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2019 ftdoajarticles https://doi.org/10.1371/journal.pntd.0007103 2022-12-31T03:56:19Z Trypanosoma cruzi, the etiological agent of Chagas' disease, affects 8 million people predominantly living in socioeconomic underdeveloped areas. T. cruzi trypomastigotes (Ty), the classical infective stage, interact with the extracellular matrix (ECM), an obligatory step before invasion of almost all mammalian cells in different tissues. Here we have characterized the proteome and phosphoproteome of T. cruzi trypomastigotes upon interaction with ECM (MTy) and the data are available via ProteomeXchange with identifier PXD010970. Proteins involved with metabolic processes (such as the glycolytic pathway), kinases, flagellum and microtubule related proteins, transport-associated proteins and RNA/DNA binding elements are highly represented in the pool of proteins modified by phosphorylation. Further, important metabolic switches triggered by this interaction with ECM were indicated by decreases in the phosphorylation of hexokinase, phosphofructokinase, fructose-2,6-bisphosphatase, phosphoglucomutase, phosphoglycerate kinase in MTy. Concomitantly, a decrease in the pyruvate and lactate and an increase of glucose and succinate contents were detected by GC-MS. These observations led us to focus on the changes in the glycolytic pathway upon binding of the parasite to the ECM. Inhibition of hexokinase, pyruvate kinase and lactate dehydrogenase activities in MTy were observed and this correlated with the phosphorylation levels of the respective enzymes. Putative kinases involved in protein phosphorylation altered upon parasite incubation with ECM were suggested by in silico analysis. Taken together, our results show that in addition to cytoskeletal changes and protease activation, a reprogramming of the trypomastigote metabolism is triggered by the interaction of the parasite with the ECM prior to cell invasion and differentiation into amastigotes, the multiplicative intracellular stage of T. cruzi in the vertebrate host. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLOS Neglected Tropical Diseases 13 2 e0007103 |
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Open Polar |
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Directory of Open Access Journals: DOAJ Articles |
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ftdoajarticles |
language |
English |
topic |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Eliciane C Mattos Gisele Canuto Nubia C Manchola Rubens D M Magalhães Thomas W M Crozier Douglas J Lamont Marina F M Tavares Walter Colli Michael A J Ferguson Maria Júlia M Alves Reprogramming of Trypanosoma cruzi metabolism triggered by parasite interaction with the host cell extracellular matrix. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
Trypanosoma cruzi, the etiological agent of Chagas' disease, affects 8 million people predominantly living in socioeconomic underdeveloped areas. T. cruzi trypomastigotes (Ty), the classical infective stage, interact with the extracellular matrix (ECM), an obligatory step before invasion of almost all mammalian cells in different tissues. Here we have characterized the proteome and phosphoproteome of T. cruzi trypomastigotes upon interaction with ECM (MTy) and the data are available via ProteomeXchange with identifier PXD010970. Proteins involved with metabolic processes (such as the glycolytic pathway), kinases, flagellum and microtubule related proteins, transport-associated proteins and RNA/DNA binding elements are highly represented in the pool of proteins modified by phosphorylation. Further, important metabolic switches triggered by this interaction with ECM were indicated by decreases in the phosphorylation of hexokinase, phosphofructokinase, fructose-2,6-bisphosphatase, phosphoglucomutase, phosphoglycerate kinase in MTy. Concomitantly, a decrease in the pyruvate and lactate and an increase of glucose and succinate contents were detected by GC-MS. These observations led us to focus on the changes in the glycolytic pathway upon binding of the parasite to the ECM. Inhibition of hexokinase, pyruvate kinase and lactate dehydrogenase activities in MTy were observed and this correlated with the phosphorylation levels of the respective enzymes. Putative kinases involved in protein phosphorylation altered upon parasite incubation with ECM were suggested by in silico analysis. Taken together, our results show that in addition to cytoskeletal changes and protease activation, a reprogramming of the trypomastigote metabolism is triggered by the interaction of the parasite with the ECM prior to cell invasion and differentiation into amastigotes, the multiplicative intracellular stage of T. cruzi in the vertebrate host. |
format |
Article in Journal/Newspaper |
author |
Eliciane C Mattos Gisele Canuto Nubia C Manchola Rubens D M Magalhães Thomas W M Crozier Douglas J Lamont Marina F M Tavares Walter Colli Michael A J Ferguson Maria Júlia M Alves |
author_facet |
Eliciane C Mattos Gisele Canuto Nubia C Manchola Rubens D M Magalhães Thomas W M Crozier Douglas J Lamont Marina F M Tavares Walter Colli Michael A J Ferguson Maria Júlia M Alves |
author_sort |
Eliciane C Mattos |
title |
Reprogramming of Trypanosoma cruzi metabolism triggered by parasite interaction with the host cell extracellular matrix. |
title_short |
Reprogramming of Trypanosoma cruzi metabolism triggered by parasite interaction with the host cell extracellular matrix. |
title_full |
Reprogramming of Trypanosoma cruzi metabolism triggered by parasite interaction with the host cell extracellular matrix. |
title_fullStr |
Reprogramming of Trypanosoma cruzi metabolism triggered by parasite interaction with the host cell extracellular matrix. |
title_full_unstemmed |
Reprogramming of Trypanosoma cruzi metabolism triggered by parasite interaction with the host cell extracellular matrix. |
title_sort |
reprogramming of trypanosoma cruzi metabolism triggered by parasite interaction with the host cell extracellular matrix. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2019 |
url |
https://doi.org/10.1371/journal.pntd.0007103 https://doaj.org/article/9a2d59abface415f985f6452e9286cf4 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 13, Iss 2, p e0007103 (2019) |
op_relation |
https://doi.org/10.1371/journal.pntd.0007103 https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0007103 https://doaj.org/article/9a2d59abface415f985f6452e9286cf4 |
op_doi |
https://doi.org/10.1371/journal.pntd.0007103 |
container_title |
PLOS Neglected Tropical Diseases |
container_volume |
13 |
container_issue |
2 |
container_start_page |
e0007103 |
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1766343849836281856 |