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Title: Nanofocused Scanning X-ray Fluorescence Microscopy Revealing an Effect of Heterozygous Hemoglobin S and C on Biochemical Activities in Plasmodium falciparum-Infected Erythrocytes

Abstract

While there is ample evidence suggesting that carriers of heterozygous hemoglobin S and C are protected from life-threatening malaria, little is known about the underlying biochemical mechanisms at the single cell level. In this work, using nanofocused scanning X-ray fluorescence microscopy, we quantify the spatial distribution of individual elements in subcellular compartments, including Fe, S, P, Zn, and Cu, in Plasmodium falciparum-infected (P. falciparum-infected) erythrocytes carrying the wild type or variant hemoglobins. Our data indicate that heterozygous hemoglobin S and C significantly modulate biochemical reactions in parasitized erythrocytes, such as aberrant hemozoin mineralization and a delay in hemoglobin degradation. The label-free scanning X-ray fluorescence imaging has great potential to quantify the spatial distribution of elements in subcellular compartments of P. falciparum-infected erythrocytes and unravel the biochemical mechanisms underpinning disease and protective traits.

Authors:
 [1]; ORCiD logo [2];  [1];  [1];  [3];  [3];  [3]; ORCiD logo [4]; ORCiD logo [5]
  1. Heidelberg Univ. (Germany)
  2. European Synchrotron Radiation Facility (ESRF), Grenoble (France); Brookhaven National Lab. (BNL), Upton, NY (United States). National Synchrotron Light Source II (NSLS-II)
  3. Universitätsklinikum Heidelberg (Germany)
  4. The European Synchrotron Radiation Facility (ESRF), 38043 Grenoble, France
  5. Heidelberg Univ. (Germany); Kyoto Univ. (Japan)
Publication Date:
Research Org.:
Brookhaven National Lab. (BNL), Upton, NY (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Basic Energy Sciences (BES); German Research Foundation (DFG); Germany’s Excellence Strategy; Japan Society for the Promotion of Science (JSPS); Nakatani Foundation
OSTI Identifier:
1646582
Report Number(s):
BNL-216237-2020-JAAM
Journal ID: ISSN 0003-2700
Grant/Contract Number:  
SC0012704; SFB1129 P3; 2082/1-390761711
Resource Type:
Accepted Manuscript
Journal Name:
Analytical Chemistry
Additional Journal Information:
Journal Volume: 92; Journal Issue: 8; Journal ID: ISSN 0003-2700
Publisher:
American Chemical Society (ACS)
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; Elements; Infectious diseases; Peptides and proteins; Fluorescence; Parasites

Citation Formats

Fröhlich, Benjamin, Yang, Yang, Thoma, Judith, Czajor, Julian, Lansche, Christine, Sanchez, Cecilia, Lanzer, Michael, Cloetens, Peter, and Tanaka, Motomu. Nanofocused Scanning X-ray Fluorescence Microscopy Revealing an Effect of Heterozygous Hemoglobin S and C on Biochemical Activities in Plasmodium falciparum-Infected Erythrocytes. United States: N. p., 2020. Web. doi:10.1021/acs.analchem.9b05111.
Fröhlich, Benjamin, Yang, Yang, Thoma, Judith, Czajor, Julian, Lansche, Christine, Sanchez, Cecilia, Lanzer, Michael, Cloetens, Peter, & Tanaka, Motomu. Nanofocused Scanning X-ray Fluorescence Microscopy Revealing an Effect of Heterozygous Hemoglobin S and C on Biochemical Activities in Plasmodium falciparum-Infected Erythrocytes. United States. https://doi.org/10.1021/acs.analchem.9b05111
Fröhlich, Benjamin, Yang, Yang, Thoma, Judith, Czajor, Julian, Lansche, Christine, Sanchez, Cecilia, Lanzer, Michael, Cloetens, Peter, and Tanaka, Motomu. Mon . "Nanofocused Scanning X-ray Fluorescence Microscopy Revealing an Effect of Heterozygous Hemoglobin S and C on Biochemical Activities in Plasmodium falciparum-Infected Erythrocytes". United States. https://doi.org/10.1021/acs.analchem.9b05111. https://www.osti.gov/servlets/purl/1646582.
@article{osti_1646582,
title = {Nanofocused Scanning X-ray Fluorescence Microscopy Revealing an Effect of Heterozygous Hemoglobin S and C on Biochemical Activities in Plasmodium falciparum-Infected Erythrocytes},
author = {Fröhlich, Benjamin and Yang, Yang and Thoma, Judith and Czajor, Julian and Lansche, Christine and Sanchez, Cecilia and Lanzer, Michael and Cloetens, Peter and Tanaka, Motomu},
abstractNote = {While there is ample evidence suggesting that carriers of heterozygous hemoglobin S and C are protected from life-threatening malaria, little is known about the underlying biochemical mechanisms at the single cell level. In this work, using nanofocused scanning X-ray fluorescence microscopy, we quantify the spatial distribution of individual elements in subcellular compartments, including Fe, S, P, Zn, and Cu, in Plasmodium falciparum-infected (P. falciparum-infected) erythrocytes carrying the wild type or variant hemoglobins. Our data indicate that heterozygous hemoglobin S and C significantly modulate biochemical reactions in parasitized erythrocytes, such as aberrant hemozoin mineralization and a delay in hemoglobin degradation. The label-free scanning X-ray fluorescence imaging has great potential to quantify the spatial distribution of elements in subcellular compartments of P. falciparum-infected erythrocytes and unravel the biochemical mechanisms underpinning disease and protective traits.},
doi = {10.1021/acs.analchem.9b05111},
journal = {Analytical Chemistry},
number = 8,
volume = 92,
place = {United States},
year = {Mon Mar 23 00:00:00 EDT 2020},
month = {Mon Mar 23 00:00:00 EDT 2020}
}

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