Presentation Title

New Antimicrobial Compounds Derived from the Sea

Presenter Information

Alexander WallickFollow

Advisor Information

Dr. Paul H. Davis

Location

249

Presentation Type

Oral Presentation

Start Date

1-3-2019 12:45 PM

End Date

1-3-2019 2:00 PM

Abstract

Toxoplama gondii is an obligate intracellular parasite infecting one third of the world’s population and is a major risk to pregnant or immunocompromised individuals. Increasing rates of pharmaceutical resistance in addition to the adverse side effects of common antiparasitic therapies have led to a need for the development of new compounds designed to treat toxoplasmosis. To meet this need, we conducted screening of several marinopyrroles isolated from marine Streptomyces that have previously shown efficacy against MRSA as well as cancerous cells. The screen consisted of treating both host cells and T. gondii infected host cells with varying concentrations of each compound to determine the compounds safety as well as their efficacy against T. gondii. From this screen, we identified 9 potential new anti-toxoplasmosis compounds with IC50 values ranging from 0.03-0.70µM compared to the control pyrimethamine which has an IC50 of 1.5µM. With these results validating further analyses, we attempted to elucidate whether these compounds functioned through the targeting of extracellular T. gondii parasites or through the modification of host cells to more effectively combat parasite invasion. Our results suggested that these compounds had no effect on either extracellular T. gondii parasites or uninfected host cells, meaning that it is possible that these compounds act against infected host cells or intracellular parasites. To further evaluate compound safety, we examined the effects of these compounds on host cell growth and proliferation. From this test, we found that 5 of the 9 drugs had no effect on U2OS (osteocarsimona cell line) proliferation

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Mar 1st, 12:45 PM Mar 1st, 2:00 PM

New Antimicrobial Compounds Derived from the Sea

249

Toxoplama gondii is an obligate intracellular parasite infecting one third of the world’s population and is a major risk to pregnant or immunocompromised individuals. Increasing rates of pharmaceutical resistance in addition to the adverse side effects of common antiparasitic therapies have led to a need for the development of new compounds designed to treat toxoplasmosis. To meet this need, we conducted screening of several marinopyrroles isolated from marine Streptomyces that have previously shown efficacy against MRSA as well as cancerous cells. The screen consisted of treating both host cells and T. gondii infected host cells with varying concentrations of each compound to determine the compounds safety as well as their efficacy against T. gondii. From this screen, we identified 9 potential new anti-toxoplasmosis compounds with IC50 values ranging from 0.03-0.70µM compared to the control pyrimethamine which has an IC50 of 1.5µM. With these results validating further analyses, we attempted to elucidate whether these compounds functioned through the targeting of extracellular T. gondii parasites or through the modification of host cells to more effectively combat parasite invasion. Our results suggested that these compounds had no effect on either extracellular T. gondii parasites or uninfected host cells, meaning that it is possible that these compounds act against infected host cells or intracellular parasites. To further evaluate compound safety, we examined the effects of these compounds on host cell growth and proliferation. From this test, we found that 5 of the 9 drugs had no effect on U2OS (osteocarsimona cell line) proliferation