Distinct amino acid and lipid perturbations characterize acute versus chronic malaria
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
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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Research Article Infectious disease Microbiology

Distinct amino acid and lipid perturbations characterize acute versus chronic malaria

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 8

Human malaria infections recapitulate acute and chronic-like metabolic profiles.

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Human malaria infections recapitulate acute and chronic-like metabolic p...
(A) Parasite asexual- and sexual-stage distribution in Thai P. falciparum cases by microscopy. (B) Spearman’s correlation of metadata for P. falciparum cases. Blue, positive correlation. Red, negative correlation. Abbreviations are as follows: gam, gametocytes per microliter by microscopy; pfs25, gametocyte gene Pfs25 marker expression by RT-PCR; temp, body temperature; pulse, heart rate/pulse in beats per minute; para, parasites per microliter by microscopy; hg, hemoglobin level; sBP, systolic blood pressure; dBP, diastolic blood pressure. (C) Venn diagram of metabolites confirmed by targeted MS/MS that significantly differ between acute and chronic malaria in rhesus macaques and humans (P < 0.05 by 2-tailed t test). Orange indicates acute malaria, and green indicates chronic malaria. (D–K) Dot plots of the concentration of metabolites in plasma in rhesus macaques (baseline, acute, chronic) and in humans (healthy, acute P.f., chronic P.f.), showing mean and SEM and including arginine (D and E), lysoPC 18:2 (F and G), C3-DC (H and I), and SM-OH C14:1 (J and K). *P < 0.05; **P < 0.01; ***P < 0.001 by 2-tailed t test.