Comparative lipidomic profiling of African trypanosomes reveals metabolic distinctions impacting pan-species drug development
5 affiliations
- 1School of Infection and Immunity, University of Glasgow, Glasgow, United Kingdom
- 2Shared Research Facilities (SRF), MVLS, University of Glasgow, Glasgow, United Kingdom
- 3Division of Biomedical Sciences, University of the Highlands and Islands, Centre for Health Sciences, Inverness, United Kingdom
- 4The Roslin Institute, Royal (Dick) School of Veterinary Studies, University of Edinburgh, Midlothian, United Kingdom
- 5Schools of Chemistry and Biology, Biomedical Sciences Research Complex, University of St Andrews, St Andrews, United Kingdom
Abstract
African trypanosomes are a group of pathogens that cause disease in humans (human African trypanosomiasis; HAT) and animals (African animal trypanosomosis; AAT) across sub-Saharan Africa, leading to profound impacts on human health as well as economic instability. Achieving sustainable disease control requires a One Health approach, yet the development of urgently required pan-species chemotherapeutics is severely hindered by a lack of unified biological understanding of the causative species. A major bottleneck in drug discovery is the distinct in vitro requirements of the clinically relevant species. Whilst Trypanosoma brucei is typically cultured in FBS-supplemented culture, T. congolense, the primary cause of AAT, requires the use of goat serum. The differing serum supplementation requirements of these two trypanosome species point to metabolic distinctions, which may be important considerations in developing experimental systems to enable the identification and design of novel, pan-species therapies. In this study, untargeted LC-MS lipidomics analyses were conducted to determine the relative lipidomic profiles of T. brucei and T. congolense bloodstream form parasites. The use of a novel medium formulation that permits effective in vitro culture of both species revealed that their lipidomic profiles are distinct. Notably, ether phospholipids, key molecules in T. brucei lipid biology, are relatively absent in T. congolense. Furthermore, the T. brucei lipidome is enriched with shorter chain saturated lipids, whilst T. congolense exhibits a preference for longer-chain polyunsaturated fatty acids (PUFAs). These observations indicate that there are significant differences in the ways these parasites synthesise and remodel their lipid complement, highlighting an evolutionary divergence between the species that likely carries implications for host-pathogen interactions as well as trypanosome membrane biology. Crucially, defining the species-specific lipid dependencies provides the foundation for pan-species culture systems, thereby removing a critical barrier to the discovery and design of novel therapeutics effective against all African trypanosome species. Author summary: African trypanosomes are a group of neglected parasites that can infect both humans and animals. The resulting diseases cause severe health impacts and billion-dollar economic losses across sub-Saharan Africa, where the diseases are prevalent. Controlling these diseases requires a One Health approach whereby both the human and animal diseases are targeted simultaneously. However, the development of new drugs is hindered by a lack of understanding of the biological commonalities and differences between the main disease-causing trypanosome species. Furthermore, the human-infective (Trypanosoma brucei) and primary animal-infective (Trypanosoma congolense) species require completely different conditions to survive in the laboratory. In this work, we aimed to determine whether differences in the ways these species use lipids explains their differing laboratory culture requirements. Using a newly designed media formulation, it was possible to culture mammalian-infective forms of both parasite species under identical conditions, enabling direct comparison of their lipidome - a complete inventory of the different fats and lipids the cells contain. We demonstrate that the T. brucei lipidome significantly differs from that of T. congolense, and that T. congolense shows a preference for longer, more unsaturated lipids. These differences are likely to underlie species-specific differences observed during host infections, and likely explains why T. brucei exhibits differential susceptibility to certain drugs and metabolic inhibitors compared to T. congolense. Furthermore, our work demonstrates that understanding the lipid biology of protozoan parasites aids in optimisation of laboratory culturing conditions, thereby facilitating further research into these understudied pathogens, including the development of new therapies aimed at all disease-causing trypanosome species.
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BibTeX
@article{dickie2026comparative,
title = {{Comparative lipidomic profiling of African trypanosomes reveals metabolic distinctions impacting pan-species drug development}},
author = {Emily A. Dickie and Stefan K. Weidt and Jennifer Haggarty and Gavin Blackburn and Mary K. Doherty and Ryan Ritchie and Edith Paxton and Simon Young and Phillip D. Whitfield and Terry K. Smith and Liam J. Morrison and Michael P. Barrett and Pieter C. Steketee},
journal = {PLOS Neglected Tropical Diseases},
year = {2026},
month = sep,
doi = {10.1371/journal.pntd.0014771},
url = {https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0014771},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Comparative lipidomic profiling of African trypanosomes reveals metabolic distinctions impacting pan-species drug development
AU - Emily A. Dickie
AU - Stefan K. Weidt
AU - Jennifer Haggarty
AU - Gavin Blackburn
AU - Mary K. Doherty
AU - Ryan Ritchie
AU - Edith Paxton
AU - Simon Young
AU - Phillip D. Whitfield
AU - Terry K. Smith
AU - Liam J. Morrison
AU - Michael P. Barrett
AU - Pieter C. Steketee
PY - 2026
DA - 2026/09/24
JO - PLOS Neglected Tropical Diseases
DO - 10.1371/journal.pntd.0014771
UR - https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0014771
AB - African trypanosomes are a group of pathogens that cause disease in humans (human African trypanosomiasis; HAT) and animals (African animal trypanosomosis; AAT) across sub-Saharan Africa, leading to profound impacts on human health as well as economic instability. Achieving sustainable disease control requires a One Health approach, yet the development of urgently required pan-species chemotherapeutics is severely hindered by a lack of unified biological understanding of the causative species. A major bottleneck in drug discovery is the distinct in vitro requirements of the clinically relevant species. Whilst Trypanosoma brucei is typically cultured in FBS-supplemented culture, T. congolense, the primary cause of AAT, requires the use of goat serum. The differing serum supplementation requirements of these two trypanosome species point to metabolic distinctions, which may be important considerations in developing experimental systems to enable the identification and design of novel, pan-species therapies. In this study, untargeted LC-MS lipidomics analyses were conducted to determine the relative lipidomic profiles of T. brucei and T. congolense bloodstream form parasites. The use of a novel medium formulation that permits effective in vitro culture of both species revealed that their lipidomic profiles are distinct. Notably, ether phospholipids, key molecules in T. brucei lipid biology, are relatively absent in T. congolense. Furthermore, the T. brucei lipidome is enriched with shorter chain saturated lipids, whilst T. congolense exhibits a preference for longer-chain polyunsaturated fatty acids (PUFAs). These observations indicate that there are significant differences in the ways these parasites synthesise and remodel their lipid complement, highlighting an evolutionary divergence between the species that likely carries implications for host-pathogen interactions as well as trypanosome membrane biology. Crucially, defining the species-specific lipid dependencies provides the foundation for pan-species culture systems, thereby removing a critical barrier to the discovery and design of novel therapeutics effective against all African trypanosome species. Author summary: African trypanosomes are a group of neglected parasites that can infect both humans and animals. The resulting diseases cause severe health impacts and billion-dollar economic losses across sub-Saharan Africa, where the diseases are prevalent. Controlling these diseases requires a One Health approach whereby both the human and animal diseases are targeted simultaneously. However, the development of new drugs is hindered by a lack of understanding of the biological commonalities and differences between the main disease-causing trypanosome species. Furthermore, the human-infective (Trypanosoma brucei) and primary animal-infective (Trypanosoma congolense) species require completely different conditions to survive in the laboratory. In this work, we aimed to determine whether differences in the ways these species use lipids explains their differing laboratory culture requirements. Using a newly designed media formulation, it was possible to culture mammalian-infective forms of both parasite species under identical conditions, enabling direct comparison of their lipidome - a complete inventory of the different fats and lipids the cells contain. We demonstrate that the T. brucei lipidome significantly differs from that of T. congolense, and that T. congolense shows a preference for longer, more unsaturated lipids. These differences are likely to underlie species-specific differences observed during host infections, and likely explains why T. brucei exhibits differential susceptibility to certain drugs and metabolic inhibitors compared to T. congolense. Furthermore, our work demonstrates that understanding the lipid biology of protozoan parasites aids in optimisation of laboratory culturing conditions, thereby facilitating further research into these understudied pathogens, including the development of new therapies aimed at all disease-causing trypanosome species.
SN - 1935-2735
ER -