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Host triacylglycerols shape the lipidome of intracellular trypanosomes and modulate their growth
Intracellular infection and multi-organ colonization by the protozoan parasite, Trypanosoma cruzi, underlie the complex etiology of human Chagas disease. While T. cruzi can establish cytosolic residence in a broad range of mammalian cell types, the molecular mechanisms governing this process remain...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5760102/ https://www.ncbi.nlm.nih.gov/pubmed/29281741 http://dx.doi.org/10.1371/journal.ppat.1006800 |
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author | Gazos-Lopes, Felipe Martin, Jessica L. Dumoulin, Peter C. Burleigh, Barbara A. |
author_facet | Gazos-Lopes, Felipe Martin, Jessica L. Dumoulin, Peter C. Burleigh, Barbara A. |
author_sort | Gazos-Lopes, Felipe |
collection | PubMed |
description | Intracellular infection and multi-organ colonization by the protozoan parasite, Trypanosoma cruzi, underlie the complex etiology of human Chagas disease. While T. cruzi can establish cytosolic residence in a broad range of mammalian cell types, the molecular mechanisms governing this process remain poorly understood. Despite the anticipated capacity for fatty acid synthesis in this parasite, recent observations suggest that intracellular T. cruzi amastigotes may rely on host fatty acid metabolism to support infection. To investigate this prediction, it was necessary to establish baseline lipidome information for the mammalian-infective stages of T. cruzi and their mammalian host cells. An unbiased, quantitative mass spectrometric analysis of lipid fractions was performed with the identification of 1079 lipids within 30 classes. From these profiles we deduced that T. cruzi amastigotes maintain an overall lipid identity that is distinguishable from mammalian host cells. A deeper analysis of the fatty acid moiety distributions within each lipid subclass facilitated the high confidence assignment of host- and parasite-like lipid signatures. This analysis unexpectedly revealed a strong host lipid signature in the parasite lipidome, most notably within its glycerolipid fraction. The near complete overlap of fatty acid moiety distributions observed for host and parasite triacylglycerols suggested that T. cruzi amastigotes acquired a significant portion of their lipidome from host triacylglycerol pools. Metabolic tracer studies confirmed long-chain fatty acid scavenging by intracellular T. cruzi amastigotes, a capacity that was significantly diminished in host cells deficient for de novo triacylglycerol synthesis via the diacylglycerol acyltransferases (DGAT1/2). Reduced T. cruzi amastigote proliferation in DGAT1/2-deficient fibroblasts further underscored the importance of parasite coupling to host triacylglycerol pools during the intracellular infection cycle. Thus, our comprehensive lipidomic dataset provides a substantially enhanced view of T. cruzi infection biology highlighting the interplay between host and parasite lipid metabolism with potential bearing on future therapeutic intervention strategies. |
format | Online Article Text |
id | pubmed-5760102 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-57601022018-01-26 Host triacylglycerols shape the lipidome of intracellular trypanosomes and modulate their growth Gazos-Lopes, Felipe Martin, Jessica L. Dumoulin, Peter C. Burleigh, Barbara A. PLoS Pathog Research Article Intracellular infection and multi-organ colonization by the protozoan parasite, Trypanosoma cruzi, underlie the complex etiology of human Chagas disease. While T. cruzi can establish cytosolic residence in a broad range of mammalian cell types, the molecular mechanisms governing this process remain poorly understood. Despite the anticipated capacity for fatty acid synthesis in this parasite, recent observations suggest that intracellular T. cruzi amastigotes may rely on host fatty acid metabolism to support infection. To investigate this prediction, it was necessary to establish baseline lipidome information for the mammalian-infective stages of T. cruzi and their mammalian host cells. An unbiased, quantitative mass spectrometric analysis of lipid fractions was performed with the identification of 1079 lipids within 30 classes. From these profiles we deduced that T. cruzi amastigotes maintain an overall lipid identity that is distinguishable from mammalian host cells. A deeper analysis of the fatty acid moiety distributions within each lipid subclass facilitated the high confidence assignment of host- and parasite-like lipid signatures. This analysis unexpectedly revealed a strong host lipid signature in the parasite lipidome, most notably within its glycerolipid fraction. The near complete overlap of fatty acid moiety distributions observed for host and parasite triacylglycerols suggested that T. cruzi amastigotes acquired a significant portion of their lipidome from host triacylglycerol pools. Metabolic tracer studies confirmed long-chain fatty acid scavenging by intracellular T. cruzi amastigotes, a capacity that was significantly diminished in host cells deficient for de novo triacylglycerol synthesis via the diacylglycerol acyltransferases (DGAT1/2). Reduced T. cruzi amastigote proliferation in DGAT1/2-deficient fibroblasts further underscored the importance of parasite coupling to host triacylglycerol pools during the intracellular infection cycle. Thus, our comprehensive lipidomic dataset provides a substantially enhanced view of T. cruzi infection biology highlighting the interplay between host and parasite lipid metabolism with potential bearing on future therapeutic intervention strategies. Public Library of Science 2017-12-27 /pmc/articles/PMC5760102/ /pubmed/29281741 http://dx.doi.org/10.1371/journal.ppat.1006800 Text en © 2017 Gazos-Lopes et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Gazos-Lopes, Felipe Martin, Jessica L. Dumoulin, Peter C. Burleigh, Barbara A. Host triacylglycerols shape the lipidome of intracellular trypanosomes and modulate their growth |
title | Host triacylglycerols shape the lipidome of intracellular trypanosomes and modulate their growth |
title_full | Host triacylglycerols shape the lipidome of intracellular trypanosomes and modulate their growth |
title_fullStr | Host triacylglycerols shape the lipidome of intracellular trypanosomes and modulate their growth |
title_full_unstemmed | Host triacylglycerols shape the lipidome of intracellular trypanosomes and modulate their growth |
title_short | Host triacylglycerols shape the lipidome of intracellular trypanosomes and modulate their growth |
title_sort | host triacylglycerols shape the lipidome of intracellular trypanosomes and modulate their growth |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5760102/ https://www.ncbi.nlm.nih.gov/pubmed/29281741 http://dx.doi.org/10.1371/journal.ppat.1006800 |
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