Drug screening by crossing membranes: a novel approach to identification of trypanocides.

Trypanosomes are a group of protozoan parasites that inflict huge health and economic burdens across the globe. The African trypanosome, Trypanosoma brucei, the causative agent of sleeping sickness, has a highly sophisticated mechanism of antigenic variation that facilitates chronic survival in the mammalian host, and also all but eliminates any realistic hope for vaccination-based control. However, trypanosomes are also highly divergent organisms, with many biochemical processes setting them apart from their hosts, and there remains great optimism that these features may be exploited for development of new drugs. Unfortunately, the compounds that are in use at present are decades old and resistance has emerged. The article in this issue of the Biochemical Journal by Patham et al., a joint team from the universities of Pittsburgh and Georgia, represents one approach to exploiting this divergence. The authors of the study have exploited novel aspects of the biochemistry within the system for translocation of nascent polypeptides across the endoplasmic reticulum membrane to identify three compounds that are able to inhibit the process. They then demonstrate that these same compounds are both trypanocidal, but well tolerated by human tissue culture cells. These observations may present interesting new leads in the fight against trypanosomiasis, and potentially identify a new target that can be explored for therapeutic potential.