Modulation of host N-glycosylation machinery during Trypanosoma cruzi infection

• Grant number: 22/09915-0
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: December 01, 2022
• End date: February 28, 2025
• Field of knowledge: Biological Sciences - Biochemistry - Chemistry of Macromolecules
• Principal Investigator: Giuseppe Palmisano
• Grantee: Bruno Rafael Barboza
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 18/15549-1 - Post-translational modifications in Chagas Disease biological processes and diagnostics: novel methodological approaches and biological applications, AP.JP2

Abstract

Trypanosoma cruzi is the etiologic agent of Chagas disease, also known as American trypanosomiasis, a potentially fatal parasitic infection that affects between 6 and 8 million individuals worldwide. Although Chagas disease is mainly found in endemic regions of Latin American countries, this infection is recognized as a potentially serious emerging global health problem. During infection by T. cruzi, macrophages (phagocytic cells) are effective in controlling parasitemia but fails to completely eradicate parasites. To ensure a successful infection, T. cruzi has developed a variety of mechanisms to evade the host immune responses, including manipulation of host glycosylation that facilitates adhesion and invasion of cells, ensuring intracellular development and survival. Still in the context of glycosylation, it was previously demonstrated that possible alterations in glycosylation observed in myocardial and vascular cells (non-phagocytic) during T. cruzi infection can be attributed to the manipulation of sialic acids from host glycoproteins. Although studies have shown the modulation of host glycoproteins in T. cruzi infection, to date, the impact of infection on the host glycosylation machinery has not been explored. Therefore, the present proposal will provide: (i) a global understanding of possible modulation in the N-glycosylation machinery of human macrophages during T. cruzi infection by identifying alterations in enzymes involved in the N-glycans biosynthesis, and characterizing the (glyco)proteomic and N-glycomic profile of infected macrophages. (ii) considering the compromise of cardiac cell functions by sialic acid manipulation in T. cruzi infection, we also proposed to explore in a targeted manner the impact of T. cruzi infection on (poly)sialylation of human cardiomyocytes, in order to provide detailed evidence on the relevance of polysialylated molecules in the establishment of possible mechanisms of resistance and/or susceptibility to T. cruzi.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

MACEDO-DA-SILVA, JANAINA; ROSA-FERNANDES, LIVIA; GOMES, VINICIUS DE MORAIS; SANTIAGO, VERONICA FEIJOLI; SANTOS, DEIVID MARTINS; MOLNAR, CATARINA MARIA STANISCHESK; BARBOZA, BRUNO RAFAEL; DE SOUZA, EDMARCIA ELISA; MARQUES, RODOLFO FERREIRA; BOSCARDIN, SILVIA BEATRIZ; et al. Protein Arginylation Is Regulated during SARS-CoV-2 Infection. Viruses-Basel, v. 15, n. 2, p. 25-pg., 2023-02-01. (18/15549-1, 18/18257-1, 20/06409-1, 22/09915-0, 20/02988-7, 21/00140-3, 20/12277-0, 21/14179-9, 15/26722-8)

BARBOZA, BRUNO RAFAEL; MACEDO-DA-SILVA, JANAINA; SILVA, LAYS ADRIANNE MENDONCA TRAJANO; DE MORAIS GOMES, VINICIUS; SANTOS, DEIVID MARTINS; MARQUES-NETO, ANTONIO MOREIRA; MULE, SIMON NGAO; ANGELI, CLAUDIA BLANES; BORSOI, JULIANA; MORAES, CAROLINA BORSOI; et al. ST8Sia2 polysialyltransferase protects against infection by Trypanosoma cruzi. PLoS Neglected Tropical Diseases, v. 18, n. 9, p. 33-pg., 2024-09-01. (22/00796-9, 21/14751-4, 20/04923-0, 18/18257-1, 21/00140-3, 18/15549-1, 20/02988-7, 22/09915-0, 21/00507-4, 23/02096-7, 21/14179-9)