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

Schmidt, Jo Ann

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Description

Title

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

Author(s)

Schmidt, Jo Ann

Issue Date

2005

Doctoral Committee Chair(s)

Kuhlenschmidt, Mark S.

Department of Study

Veterinary Pathobiology

Discipline

Veterinary Pathobiology

Degree Granting Institution

University of Illinois at Urbana-Champaign

Degree Name

Ph.D.

Degree Level

Dissertation

Keyword(s)

Biology, Microbiology

Language

eng

Abstract

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.

Graduation Semester

2005

Type of Resource

text

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