Features of apoptosis in Plasmodium falciparum erythrocytic stage through a putative role of PfMCA1 metacaspase-like protein.
The ability to undergo apoptosis, previously thought to be exclusive to multicellular organisms, has been demonstrated in unicellular parasites. On the basis of an observation that Plasmodium "crisis forms" were seen in vitro after cultivation in media containing an antimalarial drug, we attempted to determine whether Plasmodium falciparum has the ability to undergo apoptosis. By use of either the apoptosis-inducer etoposide or the antimalarial chloroquine, apoptosis in Plasmodium asexual stages was evident by the observation of DNA fragmentation and disruption of transmembrane mitochondrial potential. Next, we sought to determine whether Plasmodium produces specific cysteine proteases that can induce apoptosis. We hypothesized that the 2 metacaspase-like proteins present in the Plasmodium genome contained features typical of downstream execution steps and upstream signaling pathways such caspase activation and domain recruitment. We report that one of the metacaspase genes, PF13_0289, in addition to a universally conserved catalytic cysteine and histidine dyad required for catalysis activity, contains a putative caspase recruitment domain in the N-terminal amino acid sequence. This putative P. falciparum metacaspase protein has been designated PfMCA1. Our findings offer important insights into parasite survival strategies that could open new ways for therapeutic alternatives to drug resistance.
Meslin
Benoît
B
University Claude Bernard Lyon 1, Equipe d'Acceuil 41-70, Paristology and Tropical Medicine, Faculty of Medicine, Lyon, 69373, France.
Barnadas
Céline
C
Boni
Vanessa
V
Latour
Christine
C
De Monbrison
Frédérique
F
Kaiser
Karine
K
Picot
Stéphane
S
D000595:Amino Acid Sequence; D000818:Animals; D000962:Antimalarials / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000502:physiology*; D019556:COS Cells; D020169:Caspases / Q000235:genetics / Q000502:physiology*; D002522:Chlorocebus aethiops; D002738:Chloroquine / Q000494:pharmacology; D053938:DNA Fragmentation; D005047:Etoposide / Q000494:pharmacology; D006388:Hemagglutinins / Q000378:metabolism; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000502:physiology; D008969:Molecular Sequence Data; D010802:Phylogeny; D010963:Plasmodium falciparum / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D013997:Time Factors
D000962:Antimalarials; D000972:Antineoplastic Agents, Phytogenic; D006388:Hemagglutinins; D005047:Etoposide; D002738:Chloroquine; D020169:Caspases