Daniel Goldberg, M.D., Ph.D. Protein Export in Intraerythrocytic Malaria Parasites

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Wednesday, March 2, 2016
4:00 P.M.
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iochemistry
olecular
iophysics
Protein Export in
Intraerythrocytic Malaria Parasites
Daniel Goldberg, M.D., Ph.D.
Infectious Diseases Division
Department of Medicine
Washington University in St. Louis School of Medicine
To mediate its survival and virulence the malaria parasite Plasmodium falciparum exports hundreds of
proteins into the host erythrocyte. We have found that the export process requires a ClpB-like AAA+
ATPase called heat shock protein 101 (HSP101). We are defining the cellular and biochemical function of
this key chaperone. We are also interested in establishing the function of the exported effector proteins.
One such protein is histidine-rich protein II (HRPII). Plasma HRPII accumulates in the blood of patients
with falciparum malaria and is a diagnostic and prognostic marker. Using a human cerebral
microvascular endothelial blood-brain barrier (BBB) model, we have found that HRPII activates the
inflammasome, resulting in decreased integrity of tight junctions and increased permeability.
Intravenous administration of HRPII induces vascular leakage in the brains of mice, tight junction protein
redistribution and increased early mortality from P. berghei experimental cerebral malaria. We propose
that HRPII is a virulence factor that contributes to cerebral malaria by compromising BBB integrity.
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