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.