Anti-Plasmodium properties of group IA, IB, IIA and III secreted phospholipases A2 are serum-dependent.
Antibacterial, antiparasitidal and antiviral properties have recently been attributed to members of the secreted phospholipases A(2) (sPLA(2)s) superfamily. Seven sPLA(2)s from groups IA, IB, IIA and III, were tested here in different culture conditions for inhibition of the in vitro intraerythrocytic development of Plasmodium falciparum, the causative agent of the most severe form of human malaria. In the presence of human serum, all sPLA(2)s were inhibitory, with three out of seven exhibiting IC(50)<0.1 nM. In all cases, inhibition could be induced by enzymatic pre-treatment of the serum. By contrast, no effect was observed when parasites were grown in a semi-defined medium (AlbuMAX II) devoid of lipoproteins and containing 10 times less phospholipids than the medium with human serum, strongly suggesting that hydrolysis of serum generating toxic lipid by-products, rather than a direct interaction of the sPLA(2) with the infected erythrocyte, is a general feature of the anti-Plasmodium properties of sPLA(2)s. Furthermore, in serum, six out of the seven sPLA(2)s were toxic against both trophozoite and schizont stages of the parasite development, contrasting with the trophozoite-selective bee venom enzyme's toxicity. Deciphering the molecular mechanisms at play in the phenotypic singularity of the bee venom enzyme toxicity might offer new prospects in antimalarial fight.
Guillaume
Carole
C
USM 0504, Biologie Fonctionnelle des Protozoaires, Laboratoire de Biologie Parasitaire, Muséum National d'Histoire Naturelle, 61 rue Buffon, 75231 Paris cedex 05, France.
Deregnaucourt
Christiane
C
Clavey
Véronique
V
Schrével
Joseph
J
D000818:Animals; D000962:Antimalarials / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D003470:Culture Media; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy; D021261:Parasitic Sensitivity Tests; D010740:Phospholipases / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000254:growth & development; D012605:Scorpions; D044967:Serum; D012910:Snake Venoms / Q000737:chemistry; D012911:Snakes
D000962:Antimalarials; D003470:Culture Media; D012910:Snake Venoms; D010740:Phospholipases