Mechanisms of growth inhibition of Phytomonas serpens by the alkaloids tomatine and tomatidine.
Phytomonas serpens are flagellates in the family Trypanosomatidae that parasitise the tomato plant (Solanum lycopersicum L.), which results in fruits with low commercial value. The tomato glycoalkaloid tomatine and its aglycone tomatidine inhibit the growth of P. serpens in axenic cultures. Tomatine, like many other saponins, induces permeabilisation of the cell membrane and a loss of cell content, including the cytosolic enzyme pyruvate kinase. In contrast, tomatidine does not cause permeabilisation of membranes, but instead provokes morphological changes, including vacuolisation. Phytomonas treated with tomatidine show an increased accumulation of labelled neutral lipids (BODYPY-palmitic), a notable decrease in the amount of C24-alkylated sterols and an increase in zymosterol content. These results are consistent with the inhibition of 24-sterol methyltransferase (SMT), which is an important enzyme that is responsible for the methylation of sterols at the 24 position. We propose that the main target of tomatidine is the sterols biosynthetic pathway, specifically, inhibition of the 24-SMT. Altogether, the results obtained in the present paper suggest a more general effect of alkaloids in trypanosomatids, which opens potential therapeutic possibilities for the treatment of the diseases caused by these pathogens.
Instituto de Bioquímica Médica Leopoldo de Meis.
Jorge Mansur
JM
Medina
Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brasil.
Juliany Cola Fernandes
JC
Rodrigues
Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, RJ, Brasil.
Otacilio C
OC
Moreira
Instituto de Bioquímica Médica Leopoldo de Meis.
Geórgia
G
Atella
Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brasil.
Wanderley de
Wd
Souza
Instituto de Bioquímica Médica Leopoldo de Meis.
Hector
H
Barrabin
D002462:Cell Membrane / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D002784:Cholesterol / Q000032:analysis; D006131:Growth Inhibitors / Q000494:pharmacology*; D018551:Solanum lycopersicum / Q000469:parasitology; D008780:Methyltransferases / Q000187:drug effects; D046529:Microscopy, Electron, Transmission; D010935:Plant Diseases / Q000469:parasitology; D013261:Sterols / Q000032:analysis / Q000096:biosynthesis; D014053:Tomatine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D014351:Trypanosomatina / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure
D006131:Growth Inhibitors; D013261:Sterols; C003677:tomatidine; D014053:Tomatine; D002784:Cholesterol; D008780:Methyltransferases; C015582:zymosterol