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.

Apoptosis-like death in parasitic protozoa

Apoptosis is an essential physiological process that plays a critical role in development and tissue homeostasis in multicellular organisms, but which is also observed in several eukaryotic microorganisms such as yeast and protozoa. Here, the authors briefly review the most used techniques to detect apoptosis in mammalian cells, especially those that can be applied to parasitic protozoa after different conditions such as drugtreatment. Apoptosis-like processes have been described in protozoa which present mitochondria, such as members of the Kinetoplastida and Apicomplexa groups as well as in protozoa which do not have a mitochondrion, as Entamoeba, Trichomonas and Giardia do. These observations are of interest from an evolutive point of view, especially due to the fact that the participation of the mitochondria in apoptosis has been extensively analyzed in several biological systems. The authors also reviewed the available data showing that several drugs in use as anti-protozoa agents, as well as others which are in the development phase, kill the protozoa through an apoptotic-like process.