ST8Sia2 polysialyltransferase protects against infection by Trypanosoma cruzi

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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 ; Moutinho-Melo, Cristiane ; Muehlenhoff, Martina ; Colli, Walter ; Marie, Suely Kazue Nagashi ; da Veiga Pereira, Lygia ; Alves, Maria Julia Manso ; Palmisano, Giuseppe

• Document type: Journal article
• Source: PLoS Neglected Tropical Diseases; v. 18, n. 9, p. 33-pg., 2024-09-01.

Abstract

Glycosylation is one of the most structurally and functionally diverse co- and post-translational modifications in a cell. Addition and removal of glycans, especially to proteins and lipids, characterize this process which has important implications in several biological processes. In mammals, the repeated enzymatic addition of a sialic acid unit to underlying sialic acids (Sia) by polysialyltransferases, including ST8Sia2, leads to the formation of a sugar polymer called polysialic acid (polySia). The functional relevance of polySia has been extensively demonstrated in the nervous system. However, the role of polysialylation in infection is still poorly explored. Previous reports have shown that Trypanosoma cruzi (T. cruzi), a flagellated parasite that causes Chagas disease (CD), changes host sialylation of glycoproteins. To understand the role of host polySia during T. cruzi infection, we used a combination of in silico and experimental tools. We observed that T. cruzi reduces both the expression of the ST8Sia2 and the polysialylation of target substrates. We also found that chemical and genetic inhibition of host ST8Sia2 increased the parasite load in mammalian cells. We found that modulating host polysialylation may induce oxidative stress, creating a microenvironment that favors T. cruzi survival and infection. These findings suggest a novel approach to interfere with parasite infections through modulation of host polysialylation. (AU)

• FAPESP's process: 22/00796-9 - Unravelling the biological role of T. cruzi protein glycosylation
• Grantee: Lays Adrianne Mendonça Trajano Silva
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 21/14751-4 - Novel mass spectrometry-based technologies for post-translational modifications analysis
• Grantee: Simon Ngao Mule
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 20/04923-0 - SARS-CoV-2 glycosylation: a blueprint structural insight for understanding COVID-19 pathogenesis
• Grantee: Giuseppe Palmisano
• Support Opportunities: Regular Research Grants
• 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
• FAPESP's process: 21/00140-3 - Understanding the role of protein arginylation in health and disease through analytical and biological approaches
• Grantee: Janaína Macedo da Silva
• 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: 20/02988-7 - Decoding the impact of microenvironment and signaling pathways in health and disease in brain, adrenal gland and kidney
• Grantee: Suely Kazue Nagahashi Marie
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 22/09915-0 - Modulation of host N-glycosylation machinery during Trypanosoma cruzi infection
• Grantee: Bruno Rafael Barboza
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 21/00507-4 - Glycosylation of SARS-CoV-2 to identify the structural characteristics of COVID-19
• Grantee: Vinícius de Morais Gomes
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 23/02096-7 - Study of the cellular and humoral immunological response of mice immunized with Alum and Poly-ICLC adjuvants associated with an RBD vaccine
• Grantee: Luis Carlos de Souza Ferreira
• Support Opportunities: Research Grants - Visiting Researcher Grant - Brazil
• FAPESP's process: 21/14179-9 - The role of the endoplasmic reticulum in viral and parasitic virulence
• Grantee: Deivid Martins Santos
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)