The Sea as a Source of Novel Antiparasitic Compounds
Primary author: Rachel Relat
Faculty sponsor: Roberta O’Connor
Primary college/unit: College of Veterinary Medicine
Cryptosporidium, an intracellular parasite that causes severe diarrhea, is now recognized as a leading cause of waterborne disease worldwide, infecting both humans and valuable livestock. Cryptosporidium infection is particularly devastating in children as it causes life-threatening diarrhea, along with developmental delays including growth stunting and cognitive impairment. Cryptosporidium is an especially important disease of immunocompromised individuals of all ages, leading to chronic, potentially fatal diarrhea. No effective treatment exists for many human or veterinary patients diagnosed with Cryptosporidium.
To address this medical imperative, we designed a high throughput screen to test thousands of unique compounds, with the goal of discovering new, potent, anti-Cryptosporidium drugs and drug scaffolds. Our collaborators at the Harbor Branch Oceanographic Institute (HBOI) have amassed a library of over 125 natural compounds, and 6500 highly enriched fractions from extracts of marine organisms. We began screening this library as it contains compounds and fractions produced by sessile oceanic animals which frequently use chemical defenses. Additionally, numerous sessile oceanic organisms are known to have endosymbionts that are likely to produce additional bioactive metabolites.
We screened greater than 3,600 partially purified extracts from the HBOI library and identified 10 extracts that effectively inhibit Cryptosporidium growth without damaging the host cells in which these parasites live. Ongoing studies indicate that some of the identified fractions may also inhibit the growth of Toxoplasma gondii, a closely related parasite. This work will significantly contribute to the goal of discovering effective treatments against Cryptosporidium specifically, and further the search for novel antiparasitic drugs.