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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

The thermal proteome stability profile of Trypanosoma cruzi in epimastigote and trypomastigote life stages

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Coutinho, Joao V. P. [1] ; Rosa-Fernandes, Livia [1] ; Mule, Simon Ngao [1] ; de Oliveira, Gilberto Santos [1] ; Manchola, Nubia Carolina [2] ; Santiago, Veronica Feijoli [1] ; Colli, Walter [2] ; Wrenger, Carsten [3] ; Manso Alves, Maria Julia [2] ; Palmisano, Giuseppe [1]
Total Authors: 10
[1] Univ Sao Paulo, Inst Biomed Sci, Dept Parasitol, GlycoProt, Sao Paulo - Brazil
[2] Univ Sao Paulo, Inst Chem, Dept Biochem, Sao Paulo - Brazil
[3] Univ Sao Paulo, Unit Drug Discovery, Dept Parasitol, Inst Biomed Sci, Sao Paulo - Brazil
Total Affiliations: 3
Document type: Journal article
Source: JOURNAL OF PROTEOMICS; v. 248, SEP 30 2021.
Web of Science Citations: 0

Trypanosoma cruzi is a flagellate protozoa being the etiological agent of Chagas disease, a neglected tropical disease, which still poses a public health problem worldwide. The intricate molecular changes during T. cruzihost interaction have been explored using different largescale omics techniques. However, protein stability is largely unknown. Thermal proteome profiling (TPP) methodology has the potential to characterize proteomewide stability highlighting key proteins during T. cruzi infection and life stage transition from the invertebrate to the mammalian host. In the present work, T. cruzi epimastigotes and trypomastigotes cell lysates were subjected to TPP workflow and analyzed by quantitative large-scale mass spectrometry-based proteomics to fit a melting profile for each protein. A total of 2884 proteins were identified and associated to 1741 melting curves being 1370 in trypomastigotes (TmAVG 53.53 degrees C) and 1279 in epimastigotes (TmAVG 50.89 degrees C). A total of 453 proteins were identified with statistically different melting profiles between the two life stages. Proteins associated to pathogenesis and intracellular transport had regulated melting temperatures. Membrane and glycosylated proteins had a higher average Tm in trypomastigotes compared to epimastigotes. This study represents the first large-scale comparison of parasite protein stability between life stages. Significance: Trypanosoma cruzi, a unicellular flagellate parasite, is the etiological agent of Chagas disease, endemic in South America and affecting more that 7 million people worldwide. There is an intense research to identify novel chemotherapeutic and diagnostic targets of Chagas disease. Proteomic approaches have helped in elucidating the quantitative proteome and PTMs changes of T. cruzi during life cycle transition and upon different biotic and abiotic stimuli. However, a comprehensive knowledge of the protein-protein interaction and protein conformation is still missing. In order to fill this gap, this manuscript elucidates the T. cruzi Y strain proteomewide thermal stability map in the epimastigote and trypomastigote life stages. Comparison between life stages showed a higher average melting temperature stability for trypomastigotes than epimastigotes indicating a host temperature adaptation. Both presented a selective thermal stability shift for cellular compartments, molecular functions and biological processes based on the T. cruzi life stage. Membrane and glycosylated proteins presented a higher thermal stability in trypomastigotes when compared to the epimastigotes. (AU)

FAPESP's process: 18/13283-4 - Discovery of biomarkers of Chagas' disease in urine using mass spectrometry techniques
Grantee:Gilberto Santos de Oliveira
Support Opportunities: Scholarships in Brazil - Doctorate
FAPESP's process: 18/15549-1 - Post-translational modifications in Chagas Disease biological processes and diagnostics: novel methodological approaches and biological applications
Grantee:Giuseppe Palmisano
Support Opportunities: Research Grants - Young Investigators Grants - Phase 2
FAPESP's process: 14/06863-3 - Post-translational modifications in cancer and parasite infection diagnosis: methodological approaches and biological implications
Grantee:Giuseppe Palmisano
Support Opportunities: Research Grants - Young Investigators Grants
FAPESP's process: 17/03966-4 - Targeting lipoic acid salvage and biosynthesis pathways in MRSA
Grantee:Carsten Wrenger
Support Opportunities: Regular Research Grants
FAPESP's process: 15/26722-8 - Drug discovery against human infectious diseases
Grantee:Carsten Wrenger
Support Opportunities: Research Projects - Thematic Grants
FAPESP's process: 17/19854-0 - Signaling pathways involved in the interaction of Trypanosoma cruzi with Extracellular Matrix isolated from distinct cell lines
Grantee:Maria Julia Manso Alves
Support Opportunities: Regular Research Grants
FAPESP's process: 17/04032-5 - Dissecting the pathogenesis of Chagas Disease by deep glycomics and glycoproteomics approaches
Grantee:Simon Ngao Mule
Support Opportunities: Scholarships in Brazil - Doctorate
FAPESP's process: 18/18257-1 - Multi-user equipment approved in grant 14/06863-3: HPLC system configured for analysis of carbohydrates, amino acidis, peptides and glycoproteins
Grantee:Giuseppe Palmisano
Support Opportunities: Multi-user Equipment Program