Submitted to: Molecular and Biochemical Parasitology
Publication Type: Peer reviewed journal
Publication Acceptance Date: 1/4/2007
Publication Date: 1/9/2007
Citation: Yarlett, N., Wu, G., Waters, W.R., Harp, J.A., Wannemuehler, M.J., Morada, M., Athanasopoulos, D., Martinez, M.P., Upton, S.J., Marton, L.J. 2007. Cryptosporidium parvum spermidine/spermine N1-acetyltransferase Exhibits Different Characteristics From the Host Enzyme. Molecular and Biochemical Parasitology. 152(2):170-180. Interpretive Summary: Cryptospordium parvum is an intestinal parasite that causes diarrheal disease in calves. This disease is costly to dairy and beef producers, and the disease can also spread to humans. There are no effective drug treatments available for this parasite. In this study, we demonstrate a new class of compounds effective in the prevention and treatment of Cryptosporidium parvum infection of mice. Further study of these compounds may lead to effective treatment and prevention strategies for controlling Cryptosporidium parvum infection of cattle.
Technical Abstract: Cryptosporidosis is a common opportunistic disease of HIV-infected individuals for which no reliable therapy exists. The parasite scavenges host derived spermine which is the substrate for spermidine:spermine N(1)-acetyltransferase (SSAT). The parasite SSAT is a homotetramer with a subunit molecular mass of 18 kDa and exhibits an Ordered Bi-Bi kinetics with a preferred substrate specificity for spermine. Conformationally restricted polyamine analogues exhibited mixed inhibiton of the CpSSAT with cis analogues having lower K(I) values and longer residence times in the enzyme active site. Cis-polyamine analogues were also effective in curing an immunocompromised mouse model infection with no toxic side effects.