Plasmodium falciparum cysteine protease falcipain-1 is not essential in erythrocytic stage malaria parasites

Puran S. Sijwali, Kentaro Kato, Karl B. Seydel, Jiri Gut, Julie Lehman, Michael Klemba, Daniel E. Goldberg, Louis H. Miller, Philip J. Rosenthal

Research output: Contribution to journalArticlepeer-review

104 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)8721-8726
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume101
Issue number23
DOIs
Publication statusPublished - 2004 Jun 8

ASJC Scopus subject areas

  • General

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