Leishmania infantum stage transition using untargeted metabolomics: an emphasis on reactive species impact
Abstract
Background: Leishmaniasis remains a major global health threat, requiring Leishmania parasites to undergo complex differentiation to survive contrasting environments between the sandfly vector (promastigote form) and the mammalian host (amastigote form). While temperature and pH are known triggers for this transition, the role of the macrophage oxidative burst, specifically reactive oxygen and nitrogen species (ROS/RNS), as signaling molecules for differentiation remains poorly understood. Methods: We employed an untargeted LC-HRMS metabolomics approach, combined with chemometric analyses to characterize the metabolic fingerprints of L. infantum procyclic promastigotes, metacyclic promastigotes, and amastigotes. Additionally, we evaluated the impact of reactive species (H 2 O 2 and NO • ) on procyclic promastigotes to determine their potency as differentiation signals.
Results: Our analysis established distinct stage-specific metabolic signatures: procyclic stages are characterized by high levels of amino acids and pyrimidine nucleotides, whereas amastigotes exhibit a lipid-dominated metabolism, particularly rich in ceramides and glycerophospholipids. Crucially, we demonstrate that reactive species, with NO • being the most potent, trigger an early metabolic reprogramming toward the amastigote profile. This transition, marked by decreased in promastigote biomarkers, such as glucose-6-phosphate, and an increased in amastigote-specific markers like PE 19:1_20:1, precedes morphological changes, suggesting that metabolic adaptation is an early event in the differentiation process. Conclusion: These findings confirm that reactive species, specifically NO • acts as a key environmental signal initiating coordinated transcriptional and metabolic shifts in L. infantum. This study provides the first integrative metabolomic map of L. infantum development and highlights the importance of host-derived chemical mediators in parasite adaptation.
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BibTeX
@article{crossay2026leishmania,
title = {{Leishmania infantum stage transition using untargeted metabolomics: an emphasis on reactive species impact}},
author = {Elise Crossay and Anne-Dominique Terrisse and Pierre Pério and Théo Villarubias and Jade Royo and Alexis Valentin and Karine Reybier},
journal = {Redox Biochemistry and Chemistry},
year = {2026},
month = oct,
doi = {10.1016/j.rbc.2026.100091},
url = {https://hal.science/hal-05796267v1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Leishmania infantum stage transition using untargeted metabolomics: an emphasis on reactive species impact
AU - Elise Crossay
AU - Anne-Dominique Terrisse
AU - Pierre Pério
AU - Théo Villarubias
AU - Jade Royo
AU - Alexis Valentin
AU - Karine Reybier
PY - 2026
DA - 2026/10/13
JO - Redox Biochemistry and Chemistry
DO - 10.1016/j.rbc.2026.100091
UR - https://hal.science/hal-05796267v1
AB - Background: Leishmaniasis remains a major global health threat, requiring Leishmania parasites to undergo complex differentiation to survive contrasting environments between the sandfly vector (promastigote form) and the mammalian host (amastigote form). While temperature and pH are known triggers for this transition, the role of the macrophage oxidative burst, specifically reactive oxygen and nitrogen species (ROS/RNS), as signaling molecules for differentiation remains poorly understood. Methods: We employed an untargeted LC-HRMS metabolomics approach, combined with chemometric analyses to characterize the metabolic fingerprints of L. infantum procyclic promastigotes, metacyclic promastigotes, and amastigotes. Additionally, we evaluated the impact of reactive species (H 2 O 2 and NO • ) on procyclic promastigotes to determine their potency as differentiation signals. Results: Our analysis established distinct stage-specific metabolic signatures: procyclic stages are characterized by high levels of amino acids and pyrimidine nucleotides, whereas amastigotes exhibit a lipid-dominated metabolism, particularly rich in ceramides and glycerophospholipids. Crucially, we demonstrate that reactive species, with NO • being the most potent, trigger an early metabolic reprogramming toward the amastigote profile. This transition, marked by decreased in promastigote biomarkers, such as glucose-6-phosphate, and an increased in amastigote-specific markers like PE 19:1_20:1, precedes morphological changes, suggesting that metabolic adaptation is an early event in the differentiation process. Conclusion: These findings confirm that reactive species, specifically NO • acts as a key environmental signal initiating coordinated transcriptional and metabolic shifts in L. infantum. This study provides the first integrative metabolomic map of L. infantum development and highlights the importance of host-derived chemical mediators in parasite adaptation.
SN - 2773-1766
SN - 2773-1766
ER -