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Profiling invasive Plasmodium falciparum merozoites using an integrated omics approach

The symptoms of malaria are brought about by blood-stage parasites, which are established when merozoites invade human erythrocytes. Our understanding of the molecular events that underpin erythrocyte invasion remains hampered by the short-period of time that merozoites are invasive. To address this...

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Autores principales: Kumar, Krishan, Srinivasan, Prakash, Nold, Michael J., Moch, J. Kathleen, Reiter, Karine, Sturdevant, Dan, Otto, Thomas D., Squires, R. Burke, Herrera, Raul, Nagarajan, Vijayaraj, Rayner, Julian C., Porcella, Stephen F., Geromanos, Scott J., Haynes, J. David, Narum, David L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5719419/
https://www.ncbi.nlm.nih.gov/pubmed/29215067
http://dx.doi.org/10.1038/s41598-017-17505-9
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author Kumar, Krishan
Srinivasan, Prakash
Nold, Michael J.
Moch, J. Kathleen
Reiter, Karine
Sturdevant, Dan
Otto, Thomas D.
Squires, R. Burke
Herrera, Raul
Nagarajan, Vijayaraj
Rayner, Julian C.
Porcella, Stephen F.
Geromanos, Scott J.
Haynes, J. David
Narum, David L.
author_facet Kumar, Krishan
Srinivasan, Prakash
Nold, Michael J.
Moch, J. Kathleen
Reiter, Karine
Sturdevant, Dan
Otto, Thomas D.
Squires, R. Burke
Herrera, Raul
Nagarajan, Vijayaraj
Rayner, Julian C.
Porcella, Stephen F.
Geromanos, Scott J.
Haynes, J. David
Narum, David L.
author_sort Kumar, Krishan
collection PubMed
description The symptoms of malaria are brought about by blood-stage parasites, which are established when merozoites invade human erythrocytes. Our understanding of the molecular events that underpin erythrocyte invasion remains hampered by the short-period of time that merozoites are invasive. To address this challenge, a Plasmodium falciparum gamma-irradiated long-lived merozoite (LLM) line was developed and investigated. Purified LLMs invaded erythrocytes by an increase of 10–300 fold compared to wild-type (WT) merozoites. Using an integrated omics approach, we investigated the basis for the phenotypic difference. Only a few single nucleotide polymorphisms within the P. falciparum genome were identified and only marginal differences were observed in the merozoite transcriptomes. By contrast, using label-free quantitative mass-spectrometry, a significant change in protein abundance was noted, of which 200 were proteins of unknown function. We determined the relative molar abundance of over 1100 proteins in LLMs and further characterized the major merozoite surface protein complex. A unique processed MSP1 intermediate was identified in LLM but not observed in WT suggesting that delayed processing may be important for the observed phenotype. This integrated approach has demonstrated the significant role of the merozoite proteome during erythrocyte invasion, while identifying numerous unknown proteins likely to be involved in invasion.
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spelling pubmed-57194192017-12-08 Profiling invasive Plasmodium falciparum merozoites using an integrated omics approach Kumar, Krishan Srinivasan, Prakash Nold, Michael J. Moch, J. Kathleen Reiter, Karine Sturdevant, Dan Otto, Thomas D. Squires, R. Burke Herrera, Raul Nagarajan, Vijayaraj Rayner, Julian C. Porcella, Stephen F. Geromanos, Scott J. Haynes, J. David Narum, David L. Sci Rep Article The symptoms of malaria are brought about by blood-stage parasites, which are established when merozoites invade human erythrocytes. Our understanding of the molecular events that underpin erythrocyte invasion remains hampered by the short-period of time that merozoites are invasive. To address this challenge, a Plasmodium falciparum gamma-irradiated long-lived merozoite (LLM) line was developed and investigated. Purified LLMs invaded erythrocytes by an increase of 10–300 fold compared to wild-type (WT) merozoites. Using an integrated omics approach, we investigated the basis for the phenotypic difference. Only a few single nucleotide polymorphisms within the P. falciparum genome were identified and only marginal differences were observed in the merozoite transcriptomes. By contrast, using label-free quantitative mass-spectrometry, a significant change in protein abundance was noted, of which 200 were proteins of unknown function. We determined the relative molar abundance of over 1100 proteins in LLMs and further characterized the major merozoite surface protein complex. A unique processed MSP1 intermediate was identified in LLM but not observed in WT suggesting that delayed processing may be important for the observed phenotype. This integrated approach has demonstrated the significant role of the merozoite proteome during erythrocyte invasion, while identifying numerous unknown proteins likely to be involved in invasion. Nature Publishing Group UK 2017-12-07 /pmc/articles/PMC5719419/ /pubmed/29215067 http://dx.doi.org/10.1038/s41598-017-17505-9 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Kumar, Krishan
Srinivasan, Prakash
Nold, Michael J.
Moch, J. Kathleen
Reiter, Karine
Sturdevant, Dan
Otto, Thomas D.
Squires, R. Burke
Herrera, Raul
Nagarajan, Vijayaraj
Rayner, Julian C.
Porcella, Stephen F.
Geromanos, Scott J.
Haynes, J. David
Narum, David L.
Profiling invasive Plasmodium falciparum merozoites using an integrated omics approach
title Profiling invasive Plasmodium falciparum merozoites using an integrated omics approach
title_full Profiling invasive Plasmodium falciparum merozoites using an integrated omics approach
title_fullStr Profiling invasive Plasmodium falciparum merozoites using an integrated omics approach
title_full_unstemmed Profiling invasive Plasmodium falciparum merozoites using an integrated omics approach
title_short Profiling invasive Plasmodium falciparum merozoites using an integrated omics approach
title_sort profiling invasive plasmodium falciparum merozoites using an integrated omics approach
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5719419/
https://www.ncbi.nlm.nih.gov/pubmed/29215067
http://dx.doi.org/10.1038/s41598-017-17505-9
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