Mechanisms of growth inhibition of Phytomonas serpens by the alkaloids tomatine and tomatidine

Phytomonas serpens are flagellates in the family Trypanosomatidae that parasitise thetomato plant (Solanum lycopersicum L.), which results in fruits with low commercialvalue. The tomato glycoalkaloid tomatine and its aglycone tomatidine inhibit thegrowth of P. serpens in axenic cultures. Tomatine, like many other saponins, inducespermeabilisation of the cell membrane and a loss of cell content, including thecytosolic enzyme pyruvate kinase. In contrast, tomatidine does not causepermeabilisation of membranes, but instead provokes morphological changes, includingvacuolisation. Phytomonas treated with tomatidine show an increased accumulation oflabelled neutral lipids (BODYPY-palmitic), a notable decrease in the amount ofC₂₄-alkylated sterols and an increase in zymosterol content. Theseresults are consistent with the inhibition of 24-sterol methyltransferase (SMT),which is an important enzyme that is responsible for the methylation of sterols atthe 24 position. We propose that the main target of tomatidine is the sterolsbiosynthetic pathway, specifically, inhibition of the 24-SMT. Altogether, the resultsobtained in the present paper suggest a more general effect of alkaloids intrypanosomatids, which opens potential therapeutic possibilities for the treatment ofthe diseases caused by these pathogens.