Quantitative characterization of hemozoin in Plasmodium berghei and vivax

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dc.contributor.authorPisciotta, John M.en
dc.contributor.authorScholl, Peter F.en
dc.contributor.authorShuman, Joel L.en
dc.contributor.authorShualev, Vladimiren
dc.contributor.authorSullivan, David J.en
dc.contributor.departmentFralin Life Sciences Instituteen
dc.contributor.departmentSchool of Plant and Environmental Sciencesen
dc.date.accessioned2020-01-22T01:46:22Zen
dc.date.available2020-01-22T01:46:22Zen
dc.date.issued2017-04-01en
dc.date.updated2020-01-22T01:46:15Zen
dc.description.abstractThe 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.en
dc.description.versionPublished versionen
dc.format.extentPages 110-119en
dc.format.extent10 page(s)en
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1016/j.ijpddr.2017.02.001en
dc.identifier.eissn2211-3207en
dc.identifier.issn2211-3207en
dc.identifier.issue1en
dc.identifier.otherS2211-3207(16)30084-7 (PII)en
dc.identifier.pmid28279945en
dc.identifier.urihttp://hdl.handle.net/10919/96532en
dc.identifier.volume7en
dc.language.isoenen
dc.publisherElsevieren
dc.relation.urihttp://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000398228400011&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=930d57c9ac61a043676db62af60056c1en
dc.rightsCreative Commons Attribution-NonCommercial-NoDerivatives 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/en
dc.subjectParasitologyen
dc.subjectPharmacology & Pharmacyen
dc.subjectHemozoinen
dc.subjectChloroquine resistanceen
dc.subjectPlasmodium bergheien
dc.subjectPlasmodium vivaxen
dc.subjectCHLOROQUINE RESISTANCEen
dc.subjectHEMOGLOBIN CATABOLISMen
dc.subjectINFECTED ERYTHROCYTESen
dc.subjectMALARIA PARASITEen
dc.subjectFALCIPARUMen
dc.subjectHEMEen
dc.subjectPROTEINen
dc.subjectPFCRTen
dc.subjectQUANTIFICATIONen
dc.subjectDEGRADATIONen
dc.subject1108 Medical Microbiologyen
dc.subject.meshLiveren
dc.subject.meshSpleenen
dc.subject.meshAnimalsen
dc.subject.meshMiceen
dc.subject.meshPlasmodium bergheien
dc.subject.meshPlasmodium falciparumen
dc.subject.meshPlasmodium vivaxen
dc.subject.meshParasitemiaen
dc.subject.meshMalariaen
dc.subject.meshMalaria, Vivaxen
dc.subject.meshChloroquineen
dc.subject.meshHemeproteinsen
dc.subject.meshAntimalarialsen
dc.subject.meshDrug Resistanceen
dc.titleQuantitative characterization of hemozoin in Plasmodium berghei and vivaxen
dc.title.serialInternational Journal for Parasitology: Drugs and Drug Resistanceen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.otherArticleen
dc.type.otherJournalen
dcterms.dateAccepted2017-02-03en
pubs.organisational-group/Virginia Tech/Agriculture & Life Sciencesen
pubs.organisational-group/Virginia Tech/Agriculture & Life Sciences/School of Plant and Environmental Sciencesen
pubs.organisational-group/Virginia Tech/University Research Institutes/Fralin Life Sciences/Durelle Scotten
pubs.organisational-group/Virginia Techen
pubs.organisational-group/Virginia Tech/University Research Institutes/Fralin Life Sciencesen
pubs.organisational-group/Virginia Tech/University Research Institutesen

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