In Vitro Interaction between Barium Chloride and Pyrimethamine against Toxoplasma gondii growth
Board Location: #43
Discipline: Biological Sciences
Subcategory: Microbiology/Immunology/Virology
Session: 1
Nicholas Haas - Department of Biological Sciences, College of Engineering and Natural Sciences, University of Tennessee at Martin, Martin, TN
Co-Author(s): Kaya N. Black, Department of Biology, College of Arts and Sciences, Dillard University, New Orleans, LA
Intracellular opportunistic parasites, including Toxoplasma gondii, continue to pose significant socio-economic and public health concerns globally. With challenges such as drug resistance and toxicity associated with current treatment options, there is an urgent need for the discovery of new inhibitors against this widespread protozoan parasite. Calcium is known to play a critical role in modulating various stages of the T. gondii lytic cycle within host cells. In this study, we investigated the inhibitory effects of barium, an alkaline earth metal closely related to calcium, on the T. gondii lytic cycle.Our hypothesis that barium could disrupt the lytic cycle of T. gondii was tested, and the results revealed that barium chloride (BaCl₂) exhibited greater inhibition of tachyzoite growth compared to the standard drug pyrimethamine. The half-maximal effective concentration (EC50) values for BaCl₂ were notably lower, measuring 0.055 µg/mL, 0.059 µg/mL, and 0.033 µg/mL for 24, 48, and 72 hours of interaction, respectively. In contrast, pyrimethamine displayed higher EC50 values of 0.12 µg/mL, 0.43 µg/mL, and 0.63 µg/mL for the same time intervals.Encouraged by these findings, combination testing of BaCl₂ and pyrimethamine at various ratios (1:1, 1:2, and 2:1) was conducted to explore the potential synergistic effects. Remarkably, these combinations demonstrated even lower EC50 values, with the 1:1, 1:2, and 2:1 ratios yielding values of 20 ng/mL, 5.99 ng/mL, and 4.1 ng/mL, respectively, at 72 hours of interaction. Importantly, cytotoxicity assessments revealed that BaCl₂ and its combinations were not cytotoxic at higher concentrations, such as 5 µg/mL.These compelling results shed light on the potential of barium-based compounds as novel inhibitors of the T. gondii lytic cycle. Further research, including in vivo studies, is warranted to confirm the safety and effectiveness of barium-based drugs for the treatment of T. gondii infections, offering promising prospects for addressing this global public health concern.Keywords: Barium ion; Pyrimethamine; synergy; inhibition; T. gondii; tachyzoite; growth
Funder Acknowledgement(s): This work was supported partly by NSF-REU (DBI-2050038) to Dr. Komal Vig (PI) and the Alabama State University through the Department of Biological Sciences and the Microbiology Ph.D. Program
Faculty Advisor: Dr. Komal Vig, komalvig@alasu.edu
Role: Over the course of this research project, I assumed a pivotal role, responsible for overseeing the entire process of cell culturing and the maintaining growth of T. gondii parasites. My role also included seeding cell plates with cells, parasites, and pharmaceutical compounds, maintaining the cells’ survival, and conducting scientific readings of the cell plates. Throughout each phase of this experiment, I carried out all tasks independently and meticulously, following the guidance provided by my mentors. My contributions were integral to the successful execution of this study.