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Published on: September 17, 2016
Polyamine metabolism in the Microsporidia
C J Bacchi1, N Yarlett, L M Weiss
1Department of Biology, Pace University, New York, NY 10038, U.S.A. cbacchi@pace.edu
Abstract:
Members of the phylum Microspora are all obligate intracellular parasites. Little is known concerning metabolic pathways in these parasites, some of which pose serious problems in immunocompromised patients. We investigated polyamine metabolism in the systemic pathogen Enterocytozoon cuniculi using intact pre-emergent spores, and cell-free preparations. We found both polyamine synthetic and interconversion pathways to be operative, as evidenced by conversion of ornithine into polyamines, and production of spermidine from spermine by pre-emergent spores. Recent developments in the antitumour field have highlighted the ability of bis-ethylated polyamine analogues to reduce polyamine levels and block growth of tumour cells. In light of enhanced polyamine uptake in Enc. cuniculi, we have begun to study bis-aryl 3-7-3 and bis-ethyl oligoamine analogues as leads for chemotherapy of microsporidia.
Insights
Researchers studied polyamine metabolism in the parasite Enterocytozoon cuniculi. This parasite causes disease in immunocompromised individuals, and new drug leads targeting its polyamine pathways are being explored.
Area of Science:
- Parasitology
- Molecular Biology
- Biochemistry
Background:
- Microsporidia are obligate intracellular parasites.
- Their metabolic pathways are poorly understood.
- Some microsporidia cause severe infections in immunocompromised patients.
Purpose of the Study:
- To investigate polyamine metabolism in Enterocytozoon cuniculi.
- To identify potential therapeutic targets for microsporidial infections.
Main Methods:
- Analysis of polyamine metabolism in intact pre-emergent spores.
- Use of cell-free preparations from Enterocytozoon cuniculi.
- Investigation of polyamine synthetic and interconversion pathways.
Main Results:
- Both polyamine synthesis and interconversion pathways are active in Enterocytozoon cuniculi.
- Ornithine is converted into polyamines.
- Spermidine is produced from spermine by spores.
- Enterocytozoon cuniculi exhibits enhanced polyamine uptake.
Conclusions:
- Polyamine metabolism is a viable target for anti-microsporidial chemotherapy.
- Bis-aryl and bis-ethyl oligoamine analogues show promise as therapeutic leads.
- Further research into these analogues could lead to new treatments for microsporidiosis.
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