Investigation of novel drug therapy of KG4 for Toxoplasma gondii infections

Toxoplasma gondii is an extremely common parasite of both animals and humans, infecting an estimated up to 40% of the United States human population, but as much as 50% to 80% of the population in much of South America and continental Europe. In a healthy adult, infection with T. gondii generally results in minimal or no clinical symptoms due to a robust immune system efficiently suppressing the active form of the parasite (the tachyzoite stage). Shortly after infection, however, the parasite forms cysts (the bradyzoite stage) to protect itself from the immune system, which allows for reactivation in the event of immune system depression. T. gondii infection has been identified as a leading cause of severe illness amongst immune compromised individuals and pregnant women. Recently, T. gondii has also been recognized as a threat to many animal species, including the Southern Sea Otter off the California coast. Given these global and multi-species health concerns, it is critical that we identify effective methods for treatment and control of T. gondii. To this end, the goal of this study is to investigate the mechanism of action of the novel drug, KG4, against Toxoplasma gondii infection. We will utilize mutagenesis coupled with genomic sequencing techniques to help identify the gene targeted by KG4 to restrict T. gondii growth. Such information will be beneficial not only for the clinical use of this drug in treating patients worldwide for T. gondii infection, but will also progress our understanding of the parasite for future studies