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United States Department of Agriculture

Agricultural Research Service

Title: Novel Synthetic Polyamine Analog Chemotherapy of Cryptosporidium Parvum Infection

item Waters, Wade
item Harp, James
item Wannemuehler, M - IOWA STATE UNIV., AMES
item Marton, L - S'LIL BIOMEDICAL, WI
item Frydman, B - S'LIL BIOMEDICAL, WI

Submitted to: Research Workers in Animal Diseases Conference Proceedings
Publication Type: Abstract Only
Publication Acceptance Date: November 13, 2000
Publication Date: N/A

Technical Abstract: Cryptosporidium parvum is an important protozoan parasite of man and animals for which no effective chemotherapy is available. Recently, it was determined that C. parvum utilizes a polyamine biosynthetic pathway commonly used by plants and some bacteria, yet rarely used by non- photosynthetic eukaryotes. In the present study, it was determined that C. parvum possesses a proton driven transporter of polyamines that has an especially high affinity for spermine. By Hanes-Woolf kinetics analysis it was further determined that the conversion of spermine to spermidine to putrescine by C. parvum spermidine:spermine N**1-acetyltransferase is uncompetitively inhibited by the addition of conformationally-restricted spermine analogs. Spermine analogs were then tested for in vivo efficacy using a mouse model of persistent C. parvum infection. Oral treatment with spermine analogs significantly diminished C. parvum colonization in T cell receptor alpha-deficient mice. Up to 87% of analog-treated mice had no detectable parasites upon histologic evaluation. Together, these findings indicate that polyamine anti-metabolites are effective inhibitors of C. parvum infection in mice.

Last Modified: 4/19/2015
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