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Purification of Extracellular Trypanosomes, Including African, from Blood by Anion-Exchangers Diethylaminoethyl-cellulose Columns
Published on: April 6, 2019
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Acylation in trypanosomatids: an essential process and potential drug target
Amanda M Goldston1, Aabha I Sharma1, Kimberly S Paul2
1Departments of Pathology and Microbiology-Immunology, Northwestern University, Chicago, Illinois, USA.
Trends in Parasitology
|June 24, 2014
Summary
Protein acylation, including myristoylation and palmitoylation, is vital for trypanosomatid parasites. Inhibiting N-myristoyltransferase (NMT) kills parasites and cures infections, highlighting acylation as a drug target.
Area of Science:
- Biochemistry
- Parasitology
- Drug Discovery
Background:
- Fatty acylation, involving myristate and palmitate, is crucial for the survival, growth, and infectivity of trypanosomatids like Trypanosoma brucei, Trypanosoma cruzi, and Leishmania.
- Myristoylation and palmitoylation are essential for parasite development, protein localization, and function, with trypanosomatids having one N-myristoyltransferase (NMT) and multiple palmitoyl acyltransferases.
Purpose of the Study:
- To investigate the essentiality of protein acylation in trypanosomatids.
- To evaluate N-myristoyltransferase (NMT) as a potential drug target for trypanocidal therapies.
Main Methods:
- Characterization of N-myristoyltransferase (NMT) and palmitoyl acyltransferases in trypanosomatids.
- Global inhibition of protein acylation pathways.
- Genetic ablation of NMT.
- In vivo testing of NMT inhibitors in rodent models of Trypanosoma brucei infection.
Main Results:
- Global inhibition of myristoylation or palmitoylation leads to cell death in trypanosomatids.
- Genetic deletion of NMT significantly impairs parasite virulence.
- NMT inhibitors demonstrate efficacy in curing Trypanosoma brucei infections in rodents.
Conclusions:
- Protein acylation is indispensable for trypanosomatid viability and infectivity.
- NMT is a validated and promising drug target for developing novel trypanocidal agents.
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