Lipid and fatty acid metabolism in trypanosomatids

Abstract

Trypanosomiases and leishmaniases are neglected tropical diseases that have been spreading to previously non-affected areas in recent years. Identification of new chemotherapeutics is needed as there are no vaccines and the currently available treatment options are highly toxic and often ineffective. The causative agents for these diseases are the protozoan parasites of the Trypanosomatidae family, and they alternate between invertebrate and vertebrate hosts during their life cycles. Hence, these parasites must be able to adapt to different environments and compete with their hosts for several essential compounds, such as amino acids, vitamins, ions, carbohydrates, and lipids. Among these nutrients, lipids and fatty acids (FAs) are essential for parasite survival. Trypanosomatids require massive amounts of FAs, and they can either synthesize FAs de novo or scavenge them from the host. Moreover, FAs are the major energy source during specific life cycle stages of T. brucei, T. cruzi, and Leishmania. Therefore, considering the distinctive features of FAs metabolism in trypanosomatids, these pathways could be exploited for the development of novel antiparasitic drugs. In this review, we highlight specific aspects of lipid and FA metabolism in the protozoan parasites T. brucei, T. cruzi, and Leishmania spp., as well as the pathways that have been explored for the development of new chemotherapies.

Transcriptional Shift and Metabolic Adaptations during Leishmania Quiescence Using Stationary Phase and Drug Pressure as Models

“…Amastigotes secrete GP63 to cleave host proteins, such as fibronectin in the extracellular matrix, that in turn decreases the production of ROS by other parasite-infected macrophages [70]. Thus, GP63 upregulation in quiescent cells could be related to its many mechanisms to protect against innate immune responses to facilitate an effective infection and long-term survival within the mammalian and insect hosts [71,72].…”

Transcriptional shift and metabolic adaptations during Leishmania quiescence using stationary-phase and drug pressure as models

“…Quiescent cells also had a trend of increased levels of free fatty acids despite the downregulation of transcripts associated with the fatty acid biosynthesis across all quiescent conditions. This is not all surprising as Leishmania can switch from de novo synthesis to salvage from the host (or the medium in vitro) for the maintenance of their pool of fatty acids and lipids [68]. Moreover, the potential of a link between ALSP and the levels of fatty acids is another possible association between our transcriptomics and metabolomics findings that requires further exploration.…”

Transfer RNA-Derived Small RNAs in the Pathogenesis of Parasitic Protozoa

“…In contrast to T. cruzi , T. brucei is an extracellular parasite and undergoes cell division in the host bloodstream and the vector’s gut and salivary glands [ 41 ]. It is transmitted by the injection of infectious metacyclic trypomastigotes to the host’s skin through the bite of its vector, the tsetse fly [ 42 ]. So far, it has been known that T. brucei utilizes ribosome-associated non-coding RNAs (rancRNAs) in regulating translation in response to various forms of stress [ 43 ].…”