Tryp-ing up metabolism: role of metabolic adaptations in kinetoplastid disease pathogenesis

Today, more than a billion people - one-sixth of the world's population - are suffering from neglected tropical diseases. Human African trypanosomiasis, Chagas disease, and leishmaniasis are neglected tropical diseases caused by protozoan parasites belonging to the genera Trypanosoma and Leishmania. About half a million people living in tropical and subtropical regions of the world are at risk of contracting one of these three infections. Kinetoplastids have complex life cycles with different morphologies and unique physiological requirements at each lifecycle stage. This review covers the latest findings on metabolic pathways impacting disease pathogenesis of kinetoplastids within the mammalian host. Nutrient availability is a key factor shaping in vivo parasite metabolism; thus, kinetoplastids display significant metabolic flexibility. Proteomic and transcriptomic profiles show that intracellular trypanosomatids are able to switch to an energy-efficient metabolism within the mammalian host system. Host metabolic changes can also favor parasite persistence, and contribute to symptom development, in a location-specific fashion. Ultimately, targeted and untargeted metabolomics studies have been a valuable approach to elucidate the specific biochemical pathways affected by infection within the host, leading to translational drug development and diagnostic insights.