Nutrient acquisition at the membrane interface: Trypanosomatids subverting host defenses

Trypanosoma brucei, Trypanosoma cruzi, and Leishmania spp. are the trypanosomatid parasites responsible for some of the most significant neglected tropical diseases, such as trypanosomiases and leishmaniases, which impact millions of people globally. Alarmingly, some of these diseases have expanded into previously unaffected regions in recent years. These parasites alternate between invertebrate and vertebrate hosts during their life cycles, adapting to different environments and competing with their hosts for several nutrients. To survive, they have evolved complex strategies to acquire essential nutrients, often subverting host immune defenses and overcoming host-imposed nutritional barriers. This chapter explores the membrane-dependent mechanisms of nutrient sensing and uptake in T. brucei, T. cruzi, and Leishmania spp., with an emphasis on how these parasites adapt to nutrient-limited conditions within their host. Following an overview of the challenges posed by host imposed nutrient restrictions, we examine the parasites' membrane-associated processes and metabolic adaptations that enable their survival. The chapter spans a wide range of micro- and macronutrients-lipids, fatty acids, carbohydrates, amino acids, and metals-discussing the roles of membrane proteins in nutrient scavenging, the metabolic pathways they trigger, and their physiological importance for parasite survival, growth, and infectivity. Special attention is given to the mechanisms by which these parasites evade nutritional immunity, a host defense strategy that limits nutrient availability to pathogens. By shedding light on these nutrient acquisition strategies, this chapter aims to advance our understanding of host-parasite interactions and identify potential targets for therapeutic interventions aimed at the metabolic vulnerabilities of these parasites.