Polyamines metabolism in T. cruzi wt and expression of C. fasciculata ornthine decarboxylase (ODC)

CARRILLO C; HUBER MA; CEJAS S; GONZÁLEZ NS; ALGRANATI ID

Caxambú, Brazil

Congreso; XXVIII Reunião Anual de Pesquisa em Doença de Chagas e XVII Reunião Anual de Protozoologia; 2001

Body: Plants can be parasitized by members of the Trypanosomatidae family, artificially grouped into the genus Phytomonas. Infection by these flagellates causes lethal diseases in some vegetal species of economical interest. Polyamines are present in all cellular types and are involved in cell proliferation, among other important functions. Polyamine metabolism has been proposed as an important target for potential development of antiparasitic strategies. The biosynthesis of polyamines starts with the conversion of ornithine into putrescine by the action of ornithine decarboxylase (ODC). In plants, bacteria and some kind of mammalian cells there is an alternative pathway involving arginine decarboxylase (ADC).  In this work we have demonstrated the polyamine biosynthesis from the aminoacids arginine and ornithine in promastigote flagellates belonging to the genus Phytomonas. In this study we utilized the isolate TCC-USP 066 from Jatropha macrantha’s latex. Although a great arginine decarboxilation was observed, this activity was not inhibited by the specific and irreversible ADC inhibitor DFMA and neither agmatine nor putrescine were produced. The aminoacid arginine seems to be transformed into ornithine and other undetermined compounds. The irreversible and specific ODC inhibitor DFMO inhibited the ornithine decarboxilation activity and the production of polyamines. The measurements of ODC turnover in this isolate showed that the enzyme has a half-life of 1 hour. The addition of the drug to cultures slows down the parasite proliferation during the first days but then they recover the growth rate as in the absence of the inhibitor. On the contrary, the addition of cyclohexylamine (CHA), a specific inhibitor of spermidine synthase arrested the parasite proliferation. We concluded that in promastigote forms of Phytomonas TCC066 the synthesis of polyamines is mediated by ODC but not by ADC enzyme.     This research is sponsored by: CIC-FOMEC-CONICET.