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Genetic ablation of plasmoDJ1, a multi-activity enzyme, attenuates parasite virulence and reduces oocyst production.
- Source :
-
The Biochemical journal [Biochem J] 2014 Jul 15; Vol. 461 (2), pp. 189-203. - Publication Year :
- 2014
-
Abstract
- Malaria parasites must respond to stresses and environmental signals to perpetuate efficiently during their multistage development in diverse environments. To gain insights into the parasite's stress response mechanisms, we investigated a conserved Plasmodium protein, which we have named plasmoDJ1 on the basis of the presence of a putative cysteine protease motif of the DJ-1/PfpI superfamily, for its activities, potential to respond to stresses and role in parasite development. PlasmoDJ1 is expressed in all intraerythrocytic stages and ookinetes. Its expression was increased 7-9-fold upon heat shock and oxidative stress due to H2O2 and artemisinin; its expression in a stress-sensitive Escherichia coli mutant conferred tolerance against oxidative stress, indicating that plasmoDJ1 has the potential to sense and/or protect from stresses. Recombinant plasmoDJ1 efficiently neutralized H2O2, facilitated renaturation of denatured citrate synthase and showed protease activity, indicating that plasmoDJ1 is a multi-activity protein. Mutation of the catalytic cysteine residue, but not other residues, reduced H2O2-neutralization activity by ~90% and significantly decreased chaperone and protease activities, indicating that these activities are intrinsic to plasmoDJ1. The plasmoDJ1 gene knockout in Plasmodium berghei ANKA attenuated virulence and reduced oocyst production, suggesting a major role for plasmoDJ1 in parasite development, which probably depends on its multiple activities.
- Subjects :
- Adaptation, Physiological
Amino Acid Sequence
Animals
Antimalarials pharmacology
Artemisinins pharmacology
Erythrocytes drug effects
Erythrocytes parasitology
Escherichia coli genetics
Escherichia coli metabolism
Female
Gene Deletion
Humans
Hydrogen Peroxide pharmacology
Mice
Mice, Inbred BALB C
Molecular Sequence Data
Oocysts growth & development
Oxidative Stress
Plasmodium berghei drug effects
Plasmodium berghei enzymology
Plasmodium falciparum drug effects
Plasmodium falciparum enzymology
Protozoan Proteins metabolism
Reactive Oxygen Species metabolism
Sequence Alignment
Virulence
Oocysts metabolism
Plasmodium berghei genetics
Plasmodium berghei pathogenicity
Plasmodium falciparum genetics
Plasmodium falciparum pathogenicity
Protozoan Proteins genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1470-8728
- Volume :
- 461
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- The Biochemical journal
- Publication Type :
- Academic Journal
- Accession number :
- 25097910