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Updated: Oct 26, 2025
Quantification of Intracellular Growth Inside Macrophages is a Fast and Reliable Method for Assessing the Virulence of Leishmania Parasites
Published on: March 16, 2018
Metabolic stringent response in intracellular stages of Leishmania
Eleanor C Saunders1, Marijke F Sernee1, Julie E Ralton1
1Department of Biochemistry and Pharmacology, Bio21 Institute of Molecular Science and Biotechnology, University of Melbourne, Parkville, Victoria 3010, Australia.
Abstract:
Leishmania are unusual in being able to survive long-term in the mature phagolysosome compartment of macrophages and other phagocytic cells in their mammalian hosts. Key to their survival in this niche, Leishmania amastigotes switch to a slow growth state and activate a stringent metabolic response. The stringent metabolic response may be triggered by multiple stresses and is associated with decreased metabolic fluxes, restricted use of sugars and fatty acids as carbon sources and increased dependence on metabolic homeostasis pathways. Heterogeneity in expression of the Leishmania stringent response occurs in vivo reflects temporal and spatial heterogeneity in lesion tissues and includes non-dividing dormant stages. This response underpins the capacity of these parasites to maintain long-term chronic infections and survive drug treatments.
Insights
Leishmania parasites survive in macrophages by entering a dormant state and activating a stringent metabolic response. This survival strategy allows for chronic infections and resistance to drug treatments.
Area of Science:
- Parasitology
- Cell Biology
- Infectious Diseases
Background:
- Leishmania parasites reside within the hostile phagolysosome of host macrophages.
- Survival in this niche requires adaptation to stress and nutrient-limited conditions.
Purpose of the Study:
- To investigate the metabolic adaptations enabling Leishmania survival within macrophages.
- To understand the role of the stringent metabolic response in chronic Leishmania infections.
Main Methods:
- Analysis of Leishmania amastigote metabolic states in vivo.
- Characterization of gene expression and metabolic fluxes during stringent response activation.
Main Results:
- Leishmania amastigotes enter a slow-growth state and activate a stringent metabolic response.
- This response involves reduced metabolic activity, restricted carbon source utilization, and enhanced homeostasis.
- Heterogeneous expression of the stringent response correlates with parasite dormancy and tissue heterogeneity in vivo.
Conclusions:
- The stringent metabolic response is crucial for Leishmania survival in macrophages.
- This adaptation facilitates long-term chronic infections and drug resistance.
- Understanding this response offers potential targets for anti-Leishmania therapies.
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