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Distinct amino acid and lipid perturbations characterize acute versus chronic malaria
Regina Joice Cordy, … , Alberto Moreno, Mary R. Galinski
Regina Joice Cordy, … , Alberto Moreno, Mary R. Galinski
Published May 2, 2019
Citation Information: JCI Insight. 2019;4(9):e125156. https://doi.org/10.1172/jci.insight.125156.
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Research Article Infectious disease Microbiology

Distinct amino acid and lipid perturbations characterize acute versus chronic malaria

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Abstract

Chronic malaria is a major public health problem and significant challenge for disease eradication efforts. Despite its importance, the biological factors underpinning chronic malaria are not fully understood. Recent studies have shown that host metabolic state can influence malaria pathogenesis and transmission, but its role in chronicity is not known. Here, with the goal of identifying distinct modifications in the metabolite profiles of acute versus chronic malaria, metabolomics was performed on plasma from Plasmodium-infected humans and nonhuman primates with a range of parasitemias and clinical signs. In rhesus macaques infected with Plasmodium coatneyi, significant alterations in amines, carnitines, and lipids were detected during a high parasitemic acute phase and many of these reverted to baseline levels once a low parasitemic chronic phase was established. Plasmodium gene expression, studied in parallel in the macaques, revealed transcriptional changes in amine, fatty acid, lipid and energy metabolism genes, as well as variant antigen genes. Furthermore, a common set of amines, carnitines, and lipids distinguished acute from chronic malaria in plasma from human Plasmodium falciparum cases. In summary, distinct host-parasite metabolic environments have been uncovered that characterize acute versus chronic malaria, providing insights into the underlying host-parasite biology of malaria disease progression.

Authors

Regina Joice Cordy, Rapatbhorn Patrapuvich, Loukia N. Lili, Monica Cabrera-Mora, Jung-Ting Chien, Gregory K. Tharp, Manoj Khadka, Esmeralda V.S. Meyer, Stacey A. Lapp, Chester J. Joyner, AnaPatricia Garcia, Sophia Banton, ViLinh Tran, Viravarn Luvira, Siriwan Rungin, Teerawat Saeseu, Nattawan Rachaphaew, Suman B. Pakala, Jeremy D. DeBarry, MaHPIC Consortium, Jessica C. Kissinger, Eric A. Ortlund, Steven E. Bosinger, John W. Barnwell, Dean P. Jones, Karan Uppal, Shuzhao Li, Jetsumon Sattabongkot, Alberto Moreno, Mary R. Galinski

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Figure 4

Temporal fluctuations observed in amines, lipids, and carnitines.

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Temporal fluctuations observed in amines, lipids, and carnitines.
(A–D) ...
(A–D) Relative intensity data (LC-MS) across all 7 TPs and all 4 animals for 4 metabolites confirmed by LC-MS/MS (metabolite identification level 2a) significantly altered during infection; from top to bottom, metabolites shown are the M+H adducts of glutamine (A), kynurenine (B), palmitoylcarnitine (C), and lysoPC (18:1) (D). (E and F) Quantitative plasma concentration data at each clinical phase for significantly altered amino acids with a peak (E) or nadir (F) during the acute phase. Each of the amino acids shown demonstrated a statistically significant difference in plasma concentration across phases (repeat-measures ANOVA, P < 0.05, N = 3) except for Phe, which had a borderline P value of 0.054. Error bars indicate mean ± SEM per phase. Colors indicate phase: baseline (white), acute (orange), post-subRx (gray), and chronic (green). Orn ornithine; Cit, citrulline.

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