Quantitative characterization of hemozoin in Plasmodium berghei and vivax

John M. Pisciotta; Peter F. Scholl; Joel L. Shuman; Vladimir Shualev; David J. Sullivan

doi:10.1016/j.ijpddr.2017.02.001

International Journal for Parasitology: Drugs and Drug Resistance (Apr 2017)

Quantitative characterization of hemozoin in Plasmodium berghei and vivax

John M. Pisciotta,
Peter F. Scholl,
Joel L. Shuman,
Vladimir Shualev,
David J. Sullivan

Affiliations

John M. Pisciotta: Department of Molecular Microbiology and Immunology, Johns Hopkins University, Bloomberg School of Public Health, 615 N. Wolfe St., Baltimore, MD 21205-2179, USA
Peter F. Scholl: Department of Environmental Health Sciences, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205-2103, USA
Joel L. Shuman: Virginia Bioinformatics Institute, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA
Vladimir Shualev: Virginia Bioinformatics Institute, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA
David J. Sullivan: Department of Molecular Microbiology and Immunology, Johns Hopkins University, Bloomberg School of Public Health, 615 N. Wolfe St., Baltimore, MD 21205-2179, USA

DOI: https://doi.org/10.1016/j.ijpddr.2017.02.001
Journal volume & issue: Vol. 7, no. 1
pp. 110 – 119

Abstract

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The incidence and global distribution of chloroquine resistant (CR) Plasmodium vivax infection has increased since emerging in 1989. The mechanism of resistance in CR P. vivax has not been defined. The resistance likely relates to the formation and disposition of hemozoin as chloroquine's primary mechanism of action involves disruption of hemozoin formation. CR P. berghei strains, like CR P. vivax strains, are confined to reticulocyte host cells and reportedly they do not accumulate appreciable intraerythrocytic hemozoin. Reports comparing hemozoin production between P. vivax strains and CR to chloroquine sensitive (CS) P. berghei are absent. Here we compare in vivo patterns of hemozoin formation and distribution in blood, spleen and liver tissue of male Swiss mice infected with CS or CR P. berghei not treated with chloroquine and CR P. berghei also treated with chloroquine. Light microscopy, laser desorption mass spectrometry and a colorimetric hemozoin assay detect trace hemozoin in the blood of CR P. berghei infected mice but significant hemozoin accumulation in liver and spleen tissue. Field emission in lens scanning electron microscopy reveals CR P. berghei hemozoin crystals are morphologically smaller but similar to those formed by CS parasites. CR P. berghei produces approximately five-fold less total hemozoin than CS strain. Lipid analysis of CS and CR P. berghei sucrose gradient purified bloodstage hemozoin indicates a similar lipid environment around the isolated hemozoin, predominately monopalmitic glycerol and monostearic glycerol. In contrast to CR and CS P. berghei, colorimetric hemozoin analysis of P. vivax strains indicates similar amounts of hemozoin are produced despite differing chloroquine sensitivities. These results suggest CR P. berghei forms significant hemozoin which accumulates in liver and spleen tissues and that the P. vivax chloroquine resistance mechanism differs from P. berghei.

Published in International Journal for Parasitology: Drugs and Drug Resistance

ISSN: 2211-3207 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Internal medicine: Infectious and parasitic diseases
Website: http://www.journals.elsevier.com/international-journal-for-parasitology-drugs-and-drug-resistance/

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