Endogenous polyamine levels in macrophages is sufficient to support growth of Toxoplasma gondii.
Cytotoxic-activated macrophages control Toxoplasma gondii growth by producing nitric oxide (NO). However, the parasite can partially inhibit NO production. NO is generated from arginine within the polyamine biosynthetic pathway. Two enzymes of this pathway are ornithine, decarboxylase (ODC) and arginine decarboxylase (ADC). The aim of the present work was to investigate whether T. gondii is able to modulate polyamine metabolism in macrophages. Toxoplasma gondii infection did not affect basal ODC or ADC activity. However, lipopolysaccharide induced an increase in ODC activity. Polyamine-treated macrophages exhibited a T. gondii-infection index similar to controls but a higher adhesion index; the parasite did not grow in methyl-ornithine (ODC inhibitor)-treated macrophages. The parasites were able to take up putrescine with a Km of 0.92 microM, indicating the presence of a high-affinity putrescine-transporter system. Putrescine-treated T. gondii actively penetrated macrophages and Vero cells. However, NO production and lysosomal parasitophorous vacuole fusion were not inhibited. Considered together, these results demonstrate that T. gondii requires polyamines for multiplication. However, as opposed to Trypanosoma cruzi and because of a relatively high-affinity putrescine-transporter system in the parasite, constitutive macrophage levels of putrescine seem sufficient to support T. gondii survival and multiplication.
Laboratório de Ultraestrutura Celular Hertha Meyer, Instituto de Biofísica Carlos Chagas Filho, Edifício do Centro de Ciências da Sáude, Universidade Federal do Rio de Janeiro, Ilha do Fundão, Rio de Janeiro 21941-590, RJ, Brazil.
Sergio Henrique
SH
Seabra
Renato Augusto
RA
DaMatta
Fernando Garcia
FG
de Mello
Wanderley
W
de Souza
D000818:Animals; D002262:Carboxy-Lyases / Q000378:metabolism; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D006790:Host-Parasite Interactions; D017737:Macrophages, Peritoneal / Q000201:enzymology / Q000378:metabolism / Q000469:parasitology*; D008297:Male; D051379:Mice; D009569:Nitric Oxide / Q000096:biosynthesis; D009952:Ornithine / Q000378:metabolism; D009955:Ornithine Decarboxylase / Q000378:metabolism; D011073:Polyamines / Q000378:metabolism*; D011700:Putrescine / Q000378:metabolism; D013095:Spermidine / Q000378:metabolism; D014122:Toxoplasma / Q000254:growth & development*; D014709:Vero Cells
D011073:Polyamines; D009569:Nitric Oxide; D009952:Ornithine; D002262:Carboxy-Lyases; D009955:Ornithine Decarboxylase; C019722:arginine decarboxylase; D013095:Spermidine; D011700:Putrescine