Pharmacology of ciliated protozoa--drug (in)sensitivity and experimental drug (ab)use.

Most data on the effects of drugs as inhibitors, modulators, or stimulators have been collected with higher eukaryotic, mainly mammalian cells. Although in cell biological experiments with lower eukaryotes, including ciliates, the same drugs have frequently been applied, many results remained questionable for several reasons. Most drugs had to be used in unusually high concentrations. Moreover, drug effects have rarely been verified at the biochemical or molecular level. Data steadily emerging from genomics of ciliates, mainly Paramecium tetraurelia and Tetrahymena thermophila, show that drug-binding sites have only occasionally been conserved during evolution. They may vary or be totally absent in ciliate orthologs or specifically in certain paralogs. We here try to evaluate data available so far on the pharmacology of ciliates. In the future, domain analysis and drug screenings may detect compounds specifically effective in specific ciliated protozoa, including pathogenic forms, and, thus, yield an important basis not only for cell biology but also for ecotoxicology.