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Quantification of Intracellular Growth Inside Macrophages is a Fast and Reliable Method for Assessing the Virulence of Leishmania Parasites
Published on: March 16, 2018
Developmentally regulated sphingolipid degradation in Leishmania major
Ou Zhang1, Wei Xu, Agiesh Balakrishna Pillai
1Department of Biological Sciences, Texas Tech University, Lubbock, Texas, United States of America.
Plos One
|February 3, 2012
Summary
Sphingolipid degradation in Leishmania parasites has distinct roles: Inositol phosphorylceramide (IPCase) activity aids survival and acid tolerance, while sphingomyelinase (SMase) activity is crucial for mammalian infection. Both are vital for Leishmania pathogenesis.
Area of Science:
- Parasitology
- Molecular Biology
- Biochemistry
Background:
- Leishmania parasites exhibit complex life cycles, alternating between sandfly promastigotes and mammalian amastigotes.
- Sphingolipid (SL) metabolism, involving de novo synthesis and host salvage, is critical for parasite survival.
- A single enzyme, Inositol phosphoSphingolipid phospholipase C-Like (ISCL), degrades both inositol phosphorylceramide (IPC) and sphingomyelin (SM).
Purpose of the Study:
- To elucidate the distinct roles of ISCL's IPCase and SMase activities in Leishmania growth and virulence.
- To investigate the necessity of SL degradation for parasite survival in different life stages and hosts.
Main Methods:
- Generation of Leishmania major ISCL-null mutants.
- Complementation of mutants with either IPCase or SMase activity.
- Assessment of parasite survival, acid resistance, macrophage survival, and mouse virulence.
Main Results:
- Restoration of IPCase activity rescued acid resistance and macrophage survival but not mouse virulence.
- Restoration of SMase activity fully restored parasite infectivity in mice but not promastigote defects.
- ISCL expression is upregulated in stationary phase promastigotes and amastigotes.
Conclusions:
- Leishmania's SL degradation pathways have stage-specific functions: IPCase for promastigote survival and SMase for amastigote virulence.
- Distinct enzymatic activities of ISCL are essential for Leishmania to establish and maintain infection in mammalian hosts.
- Targeting SL degradation pathways could be a strategy for anti-Leishmania therapies.
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