Leveraging allelopathy for drug discovery: ocean phytoplankton metabolomes as anti-T. gondii drug candidates: a bioassay strategy 2330921

Abstract

Abstract Introduction Toxoplasma gondii is an obligate intracellular apicomplexan parasite responsible for fatal foodborne illness (toxoplasmosis) and severe neurological and cognitive defects in vulnerable populations. Current treatments, namely sulfadiazine and pyrimethamine, are ineffective and cause adverse effects. Allelopathy, the process by which phytoplankton species exude compounds to affect competitive behavior, provides a potential strategy as novel inhibitors of T. gondii. The endometabolomic and exometabolomic extracts from several phytoplankton species were screened for anti-parasitic activity. Methods Previous data suggests allelochemicals of candidate species may inhibit another apicomplexan parasite, Plasmodium falciparum. Extracts were collected using solid phase extraction, separating endometabolome and exometabolomes of select species. To determine whether these species will inhibit T. gondii invasion, MRC5 human fibroblast host cells infected with T. gondii were treated and incubated with extract treatments in a dose response curve. The T. gondii plaque assay and the MTT cell proliferation assay were used to quantify the effect of treatment on parasite invasion into MRC5 monolayers and compared to the positive control, sulfadiazine. Results Whole exometabolomes sourced from Prymnesium parvum inhibited plaque formation at a 250 µg/mL concentration, with fewer and smaller plaques compared to untreated monolayers. Preliminary analysis suggests P. parvum and Rhodomonas lens inhibit T. gondii invasion in a modest dose response curve. Conclusion Using an allelopathic inhibition approach, select phytoplankton extracts contain compounds with promising inhibition of T. gondii invasion of MRC5 human fibroblasts. Future studies will evaluate biochemically isolated phytoplankton extracts for inhibition of T. gondii and other apicomplexan parasites. Funding Source University of North Carolina at Wilmington - Center for the Support of Undergraduate Research and Fellowships Topic Categories Microbial, Parasitic, and Fungal Immunology (MPF)