Investigation of Specialized Metabolites in Apicomplexan Parasite Life Cycles

Abstract

<p>Across the tree of life, specialized metabolites mediate ecological interactions and can ultimately drive evolution. Characterization of these small molecules have led scientists to a greater comprehension of ecological niches at the macro- and micro-scale. A group of medicinally important organisms with life cycles that include various ecological niches are apicomplexan parasites. The most notorious parasites belong to the genera Plasmodium and Toxoplasma, which are responsible for malaria and toxoplasmosis, respectively. Traditional efforts to reduce malaria include pharmaceuticals and prevention of mosquito-based transmission through insecticides and bed nets. Despite this, malaria has prevailed. Efforts were devised to understand the chemical ecology surrounding malaria parasites during the mosquito stage to ultimately reduce transmission. Through structure-, bioinformatic-, and coculture-guided approaches, we have uncovered chemical space within the mosquito-microbiome and evaluated how microbial-produced small molecules influence the parasite during its vector stage. We have also expanded our knowledge of parasite-produce specialized metabolites. Within Toxoplasma parasites, we have begun to characterize a polyketide synthase (PKS) with unknown resultant products. Together, this work provides the basis for understanding how specialized metabolites within the mosquito microbiome affect the Plasmodium parasite transmission capacity while also investigating an underexplored area of natural product chemistry within Toxoplasma parasites.</p>