Fatty Acid-Mediated Inhibition of Host Cell Invasion by Cryptosporidium Parvum

We have purified from bovine colostrum digests an unsaturated fatty acid that inhibits Cryptosporidium parvum sporozoite invasion of host cells in vitro. A panel of similar lipids with varying chain lengths and degrees of saturation were tested for evidence of inhibitory activity in order to determine the range of specificity. We identified a subset of inhibitory fatty acids and investigated the structural characteristics required for anti-cryptosporidial activity. Finally, we examined potential mechanisms for the lipid-mediated inhibition of sporozoite-host cell adhesion and invasion in vitro. These mechanisms included direct cytotoxicity to host cells and/or parasites, interruption of normal signaling pathways and alterations in gene expression. Our assays showed that eighteen-carbon unsaturated and twenty-carbon polyunsaturated free fatty acids with free carboxyl ends inhibited the invasion of host enterocytes by sporozoites in vitro by blocking microneme secretion. These results indicate a potential chemotherapeutic utility for a subset of long chain unsaturated free fatty acids in the treatment of cryptosporidiosis.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Veterinary Pathobiology

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2005

Author dc:creator

• Schmidt, Jo Ann

Contributors dc:contributor

• Kuhlenschmidt, Mark S.

• Biology, Microbiology

Language dc:language

eng

Identifier

(MiAaPQ)AAI3199135

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/87631