Resistance as a tool in the study of old and new drug targets in Toxoplasma.

Drug resistance generated in vitro in the protozoan parasite Toxoplasma gondii is described. We focus on drugs that are in use in patients, that show some promise for such use, or that represent lead compounds for further development. No instance has yet been reported where resistance to any of these drugs has arisen in a patient or in the field although different strains do show varying degrees of sensitivity. For many of these drugs, however, resistant lines have been generated in the laboratory and these have proven very useful for elucidating a given drug's target. These targets range from metabolic pathways in the cytosol to organellar functions encoded in the mitochondrion or plastid. Such information makes predictions about how fast resistance will arise in the field but more importantly, it helps identify targets that are crucial to the parasite and predicts which combinations of drugs should act synergistically.