Target acquired: transcriptional regulators as drug targets for protozoan parasites

Protozoan parasites are single-celled eukaryotic organisms that cause significant human disease and pose a substantial health and socioeconomic burden worldwide. They are responsible for at least 1 million deaths annually. The treatment of such diseases is hindered by the ability of parasites to form latent cysts, develop drug resistance, or be transmitted by insect vectors. Additionally, these pathogens have developed complex mechanisms to alter host gene expression. The prevalence of these diseases is predicted to increase as climate change leads to the augmentation of ambient temperatures, insect ranges, and warm water reservoirs. Therefore, the discovery of novel treatments is necessary. Transcription factors lie at the junction of multiple signalling pathways in eukaryotes and aberrant transcription factor function contributes to the progression of numerous human diseases including cancer, diabetes, inflammatory disorders and cardiovascular disease. Transcription factors were previously thought to be undruggable. However, due to recent advances, transcription factors now represent appealing drug targets. It is conceivable that transcription factors, and the pathways they regulate, may also serve as targets for anti-parasitic drug design. Here, we review transcription factors and transcriptional modulators of protozoan parasites, and discuss how they may be useful in drug discovery. We also provide information on transcription factors that play a role in stage conversion of parasites, TATA box-binding proteins, and transcription factors and cofactors that participate with RNA polymerases I, II and III. We also highlight a significant gap in knowledge in that the transcription factors of some of parasites have been under-investigated. Understanding parasite transcriptional pathways and how parasites alter host gene expression will be essential in discovering innovative drug targets.