ST8Sia2 polysialyltransferase protects against infection by Trypanosoma cruzi.

Autor: Barboza BR; GlycoProteomics Laboratory, Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil., Macedo-da-Silva J; GlycoProteomics Laboratory, Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil., Silva LAMT; GlycoProteomics Laboratory, Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil., Gomes VM; GlycoProteomics Laboratory, Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil., Santos DM; GlycoProteomics Laboratory, Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil., Marques-Neto AM; GlycoProteomics Laboratory, Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil., Mule SN; GlycoProteomics Laboratory, Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil., Angeli CB; GlycoProteomics Laboratory, Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil., Borsoi J; Department of Genetics and Evolutionary Biology, Institute of Biosciences, University of São Paulo, São Paulo, Brazil., Moraes CB; Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil., Moutinho-Melo C; Laboratory of Vaccine Development, Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.; Laboratory of Immunological and Antitumor Analysis, Department of Antibiotics, Bioscience Center, and Keizo Asami Immunopathology Laboratory, Federal University of Pernambuco, Recife, Brazil., Mühlenhoff M; Institute of Clinical Biochemistry, Hannover Medical School, Hannover, Germany., Colli W; Department of Biochemistry, Institute of Chemistry, University of São Paulo, São Paulo, Brazil., Marie SKN; Laboratory of Molecular and Cellular Biology (LIM 15), Department of Neurology, School of Medicine, University of São Paulo, São Paulo, Brazil., Pereira LDV; Department of Genetics and Evolutionary Biology, Institute of Biosciences, University of São Paulo, São Paulo, Brazil., Alves MJM; Department of Biochemistry, Institute of Chemistry, University of São Paulo, São Paulo, Brazil., Palmisano G; GlycoProteomics Laboratory, Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.; School of Natural Sciences, Macquarie University, Sydney, New South Wales, Australia.
Jazyk: angličtina
Zdroj: PLoS neglected tropical diseases [PLoS Negl Trop Dis] 2024 Sep 25; Vol. 18 (9), pp. e0012454. Date of Electronic Publication: 2024 Sep 25 (Print Publication: 2024).
DOI: 10.1371/journal.pntd.0012454
Abstrakt: 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.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2024 Barboza et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Databáze: MEDLINE
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