Thesis
Boromycin has potent anti-Toxoplasma and anti-Cryptosporidium activity
Washington State University
Master of Science (MS), Washington State University
05/2020
DOI:
https://doi.org/10.7273/000004194
Handle:
https://hdl.handle.net/2376/125017
Abstract
Toxoplasma gondii and Cryptosporidium parvum, members of the phylum Apicomplexa, are considered significant pathogens of both humans and animals worldwide. They are obligate intracellular parasites that cause serious conditions like neurological abnormalities, blindness or chronic diarrhea, especially to immunocompromised individuals. Currently there are no effective therapeutics to treat cryptosporidiosis in children and no drugs that eliminate the chronic bradyzoite stage responsible for toxoplasmosis in AIDS patients, making the discovery of new therapeutic drugs a priority. Here we described the activity of boromycin, a lipid-soluble antibiotic produced by Streptomyces antibioticus, against T. gondii and C. parvum. Boromycin potently inhibited intracellular proliferation of both T. gondii and C. parvum both at nanomolar concentrations with 50% inhibitory concentration (EC50) of 2.13nM and 4.99nM, respectively. Treatment of extracellular T. gondii with 25nM of boromycin for 30 mins suppressed 84% of parasite growth, and parasites did not recover even after 96 hours of incubation post-treatment. Synchronized invasion assay also revealed a reduced in T. gondii tachyzoite invasion to host cells. Furthermore, immunofluorescence of boromycin-treated T. gondii using anti-surface antigen glycoprotein-1 (SAG1) antibodies showed loss of morphologically intact parasites with randomly distributed surface antigens inside the parasitophorous vacuoles. Cytotoxic concentration (CC50) of boromycin to HFFs and HCT-8s were 20.0 [mu]M and 27.46 [mu]M, respectively. Boromycin also displayed a high selectivity Index (SI) ranging from 3767 to 8812 which signifies a high specificity of the drug to the parasites but not to the host cells. These results suggest boromycin is a promising new drug candidate for treating toxoplasmosis and cryptosporidiosis.
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Details
- Title
- Boromycin has potent anti-Toxoplasma and anti-Cryptosporidium activity
- Creators
- Jaypee Abenoja
- Contributors
- ROBERTA OCONNOR (Advisor) - Washington State University, Veterinary Microbiology and Pathology, Department of
- Awarding Institution
- Washington State University
- Academic Unit
- Veterinary Medicine, College of
- Theses and Dissertations
- Master of Science (MS), Washington State University
- Publisher
- Washington State University
- Identifiers
- 99900896439101842
- Language
- English
- Resource Type
- Thesis