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pmid:30726203
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
PLoS neglected tropical diseases · 2019 doi:10.1371/journal.pntd.0007103
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Complete file
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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.", "claims": [{"id": "claim-method", "statement": "Statistical analysis for validation of the results was performed by T Student test (two-tail, 95%).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:30726203", "locator": "sections[11] \"Proteome and Phosphoproteome data analysis\" paragraph 2", "quote": "Statistical analysis for validation of the results was performed by T Student test (two-tail, 95%)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The mass spectrometry proteomics and phosphoproteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE [74] partner repository with the dataset identifier PXD010970.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:30726203", "locator": "sections[33] \"Acknowledgments\" paragraph 2", "quote": "The mass spectrometry proteomics and phosphoproteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE [74] partner repository with the dataset identifier PXD010970."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": null, "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:30726203"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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