@article{6c7c8a1930db4766b5af299d7af3ef50,
title = "Profiling invasive Plasmodium falciparum merozoites using an integrated omics approach",
abstract = "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.",
author = "Krishan Kumar and Prakash Srinivasan and Nold, {Michael J.} and Moch, {J. Kathleen} and Karine Reiter and Dan Sturdevant and Otto, {Thomas D.} and Squires, {R. Burke} and Raul Herrera and Vijayaraj Nagarajan and Rayner, {Julian C.} and Porcella, {Stephen F.} and Geromanos, {Scott J.} and Haynes, {J. David} and Narum, {David L.}",
note = "Funding Information: The authors thank the following people for superb technical support: Kishore Kanakabandi and Kimmo Virtaneva from Genomics Unit, Rocky Mountain Laboratories, NIAID, NIH, Hamilton, Montana, Richard Shimp, LMIV and Dr. Lisa R. Olano from the Research Technology Branch, NIAID, NIH. We thank Dr. Anthony Holder for the anti-MSP6 and anti-MSP7 antibodies. We thank Dr. Xinzhuan Su, NIAID for restriction enzyme fingerprinting of HDGFP. We thank Maureen Stefaniak, NMRC for γ-irradiating the WT parasites. We thank Jackie Williams, Jeffrey Snavely, Jack Komisar, Shannon McGrath, and Fouzia Farooq from WRAIR for supplying the HDGFP (WT) parasite line (JW), for helping with parasite culture (JS) and for advice on flow cytometry (JK, SM, and FF). We appreciated the support of Drs. Louis Miller and Patrick Duffy from the NIAID, NIH and Fred Glisson from Waters Corporation. We thank Matt Berriman and Mandy Sanders from the Wellcome Trust Sanger Institute for processing the samples for sequencing. We thank PlasmoDB.org for their helpful resource. The views expressed in this article are those of the authors and do not necessarily reflect the official policy or position of the Department of the Army, the Department of Defense, nor the U.S. Government. Material has been reviewed by the Walter Reed Army Institute of Research. There is no objection to its presentation and/or publication. This research was supported in part by the Intramural Research Program of NIAID, NIH and by the Wellcome Trust (Grant number 098051) and TDO was supported by the European Union 7th framework EVIMalar. Publisher Copyright: {\textcopyright} 2017 The Author(s).",
year = "2017",
month = dec,
day = "1",
doi = "10.1038/s41598-017-17505-9",
language = "English (US)",
volume = "7",
journal = "Scientific reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
number = "1",
}