Plasmodium Falciparum Cysteine Protease Falcipain-1 is Not Essential in Erythrocytic Stage Malaria Parasites

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2004 May 29

PMID 15166288

Citations 34

Authors

Puran S Sijwali

Kentaro Kato

Karl B Seydel

Jiri Gut

Julie Lehman

Michael Klemba

Daniel E Goldberg

Louis H Miller

Philip J Rosenthal

Affiliations

Soon will be listed here.

Abstract

Among potential new targets for antimalarial chemotherapy are Plasmodium falciparum cysteine proteases, known as falcipains. Falcipain-2 and falcipain-3 are food vacuole hemoglobinases that may have additional functions. The function of falcipain-1 remains uncertain. To better characterize the role of falcipain-1 in erythrocytic parasites, we disrupted the falcipain-1 gene and characterized recombinant parasites. Disruption of the falcipain-1 gene was confirmed with Southern blots, and loss of expression of falcipain-1 was confirmed with immunoblots and by loss of labeling with a specific protease inhibitor. Compared with wild-type parasites, falcipain-1 knockout parasites developed normally, with the same morphology, multiplication rate, and invasion efficiency, and without significant differences in sensitivity to cysteine protease inhibitors. In wild-type and knockout parasites, cysteine protease inhibitors blocked hemoglobin hydrolysis in trophozoites, with a subsequent block in rupture of erythrocytes by mature schizonts, but they did not inhibit erythrocyte invasion by merozoites. Our results indicate that although falcipain-1 is expressed by erythrocytic parasites, it is not essential for normal development during this stage or for erythrocyte invasion.

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