ORAL PRESENTATION Open Access

Stepwise dissection of Plasmodium falciparummerozoite invasion of the human erythrocyteDavid Riglar1, Dave Richard1, Michelle Boyle1, Danny Wilson1, Fiona Angrisano1, Lynne Turnbull2,Cynthia Whitchurch2, Alan Cowman1, James Beeson1, Stuart Ralph3, Jake Baum1*

From Parasite to Prevention: Advances in the understanding of malariaEdinburgh, UK. 20-22 October 2010

BackgroundA critical step in establishing malaria parasite infectionis the ability of the blood stage merozoite to invade ery-throcytes. However, much of our understanding aboutthe cell biology of this process has remained unchangedsince seminal work, more than 30 years ago, defined thesteps of entry by light and electron microscopy. Thesestudies were, however, only possible using merozoitesfrom simian and avian malaria parasite species, giventhe poor viability of merozoites from human parasites,specifically Plasmodium falciparum. In contrast, criticalinvasion proteins have been best described for humanor mouse parasite species. Thus our understandingabout the molecular and cellular coordination of theentire process of invasion is still largely unknown.Towards addressing this gap, we recently developed amethod for harvesting viable P. falciparum merozoites,permitting detailed investigation of the molecular eventsof merozoite invasion [1].

ResultsUsing super resolution and immunoelectron microscopyof P. falciparum merozoites we place the core invasionmachinery in context as the parasite enters the redblood cell. We establish that irreversible merozoiteattachment to the erythrocyte surface is the trigger forall subsequent invasion events, which include: secretionof apical rhoptries, surface-protein shedding and acto-myosin motor activation. Irreversible attachment is

therefore the master switch for merozoite entry, withthe tight junction acting as a nexus around which inva-sion is orchestrated.

ConclusionsDetailed imaging analysis allows us to propose a com-plete model for merozoite invasion and permits under-standing of not only the mechanics of invasion but alsothe mechanism of action of drug or other strategies thatperturb the process. The ability to understand this keystep in malaria disease establishment provides a generalplatform to evaluate strategies that target merozoiteentry for malaria therapy.

Author details1Walter and Eliza Hall Institute of Medical Research, Parkville Victoria 3052,Melbourne, Australia. 2iThree Institute, University of Technology Sydney,Ultimo NSW 2007, Australia. 3Bio21 Molecular Sciences and BiotechnologyInstitute, University of Melbourne, Parkville Victoria 3010, Melbourne,Australia.

Published: 20 October 2010

Reference1. Boyle MJ, Wilson DW, Richards JS, Riglar DT, Tetteh KK, Conway DJ,

Ralph SA, Baum J, Beeson JG: Isolation of viable Plasmodium falciparummerozoites to define erythrocyte invasion events and advance vaccineand drug development. Proc Natl Acad Sci U S A 2010, 107:14378-8.

doi:10.1186/1475-2875-9-S2-O25Cite this article as: Riglar et al.: Stepwise dissection of Plasmodiumfalciparum merozoite invasion of the human erythrocyte. Malaria Journal2010 9(Suppl 2):O25.

1Walter and Eliza Hall Institute of Medical Research, Parkville Victoria 3052,Melbourne, AustraliaFull list of author information is available at the end of the article

Riglar et al. Malaria Journal 2010, 9(Suppl 2):O25http://www.malariajournal.com/content/9/S2/O25

© 2010 Baum et al; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative CommonsAttribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction inany medium, provided the original work is properly cited.