Lipidomics and anti‐trypanosomatid chemotherapy

Abstract

Background Trypanosomatids such as Leishmania, Trypanosoma brucei and Trypanosoma cruzi belong to the order Kinetoplastida and are the source of many significant human and animal diseases. Current treatment is unsatisfactory and is compromised by the rising appearance of drug resistant parasites. Novel and more effective chemotherapeutics are urgently needed to treat and prevent these devastating diseases, which relies on the identification of essential, parasite specific targets that are absent in the host. Lipids constitute essential components of the cell and carry out multiple critical functions from building blocks of biological membranes to regulatory roles in signal transduction, organellar biogenesis, energy storage, and virulence. The recent technological advances of lipidomics has facilitated the broadening of our knowledge in the field of cellular lipid content, structure, functions, and metabolic pathways. Main body This review highlights the application of lipidomics (i) in the characterization of the lipidome of kinetoplastid parasites or of their subcellular structure(s), (ii) in the identification of unique lipid species or metabolic pathways that can be targeted for novel drug therapies, (iii) as an analytic tool to gain a deeper insight into the roles of specific enzymes in lipid metabolism using genetically modified microorganisms, and (iv) in deciphering the mechanism of action of anti-microbial drugs on lipid metabolism. Lastly, an outlook stating where the field is evolving is presented. Conclusion Lipidomics has contributed to the expanding knowledge related to lipid metabolism, mechanism of drug action and resistance, and pathogen–host interaction of trypanosomatids, which provides a solid basis for the development of better anti-parasitic pharmaceuticals.

Drug effects on metabolic profiles of Schistosoma mansoni adult male parasites detected by 1H-NMR spectroscopy

“…Remarkably in protozoan parasites such as Plasmodium falciparum and Trypanosoma brucei, the Kennedy pathway has already been proposed as a potentially relevant drug target [42][43][44][45][46][47][48]. Further investigation of the Kennedy metabolic pathway in S. mansoni could be important for drug discovery and drug repositioning (i.e.…”

Parasite Sensing of Host Nutrients and Environmental Cues

“…In a similar approach, a lipidomic analysis of the T. brucei procyclic (the parasite form transmitted by the tsetse fly) versus the mammalian bloodstream forms revealed significant differences in sphingolipid metabolism. While the relevance of such observation awaits clarification, the absence of some of these sphingolipid species in vertebrates strengthens the importance of such lipids in parasite biology (reviewed in Biagiotti et al, 2017). The metabolome of T. brucei procyclic forms was further analyzed by Kamleh et al, 2008, in which the authors compared the procyclic forms fed on glucose (the main carbon source) versus proline (highly abundant in the tsetse fly), providing evidence that metabolic alterations are a significant part of the parasite's adaptation to the tsetse vector.…”

“…Plasmodium, for example, has lost the ability to synthesize de novo amino acids (aa) and has devised mechanisms to scavenge aa from the catabolism of hemoglobin (Gardner et al, 2002;Olszewski et al, 2009). Trypanosoma cruzi, which completely lacks the ability to synthesize cholesterol like most parasites (reviewed in Biagiotti et al, 2017), has developed efficient ways of taking up and storing host cholesterol (Pereira et al, 2011).…”

Human Kinetoplastid Protozoan Infections: Where Are We Going Next?

“…In fact omics-based analyses have facilitated the broadening of R&D researches in the field of drug development. Lipidomics analyses have yielded the characterization of lipid structures, protein lipidation pathways in post-translational modifications, and their putative functions for kinetoplastid parasites ( 33 , 34 ). This knowledge will allow the search for new classes of anti-parasitic pharmaceuticals.…”