RESUMO
Auranofin, an FDA-approved drug for rheumatoid arthritis, has emerged as a promising antiparasitic medication in recent years. The gold(I) ion in auranofin is postulated to be responsible for its antiparasitic activity. Notably, aurothiomalate and aurothioglucose also contain gold(I), and, like auranofin, they were previously used to treat rheumatoid arthritis. Whether they have antiparasitic activity remains to be elucidated. Herein, we demonstrated that auranofin and similar derivatives, but not aurothiomalate and aurothioglucose, inhibited the growth of Toxoplasma gondii in vitro. We found that auranofin affected the T. gondii biological cycle (lytic cycle) by inhibiting T. gondii's invasion and triggering its egress from the host cell. However, auranofin could not prevent parasite replication once T. gondii resided within the host. Auranofin treatment induced apoptosis in T. gondii parasites, as demonstrated by its reduced size and elevated phosphatidylserine externalization (PS). Notably, the gold from auranofin enters the cytoplasm of T. gondii, as demonstrated by scanning transmission electron microscopy-energy dispersive X-ray spectroscopy (STEM-EDS) and Inductively Coupled Plasma-Mass Spectrometry (ICP-MS).IMPORTANCEToxoplasmosis, caused by Toxoplasma gondii, is a devastating disease affecting the brain and the eyes, frequently affecting immunocompromised individuals. Approximately 60 million people in the United States are already infected with T. gondii, representing a population at-risk of developing toxoplasmosis. Recent advances in treating cancer, autoimmune diseases, and organ transplants have contributed to this at-risk population's exponential growth. Paradoxically, treatments for toxoplasmosis have remained the same for more than 60 years, relying on medications well-known for their bone marrow toxicity and allergic reactions. Discovering new therapies is a priority, and repurposing FDA-approved drugs is an alternative approach to speed up drug discovery. Herein, we report the effect of auranofin, an FDA-approved drug, on the biological cycle of T. gondii and how both the phosphine ligand and the gold molecule determine the anti-parasitic activity of auranofin and other gold compounds. Our studies would contribute to the pipeline of candidate anti-T. gondii agents.
Assuntos
Artrite Reumatoide , Fosfinas , Toxoplasma , Toxoplasmose , Humanos , Auranofina/farmacologia , Auranofina/uso terapêutico , Ouro/farmacologia , Ouro/uso terapêutico , Ligantes , Aurotioglucose/farmacologia , Aurotioglucose/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Tiomalato Sódico de Ouro/farmacologia , Tiomalato Sódico de Ouro/uso terapêutico , Antiparasitários/farmacologia , Antiparasitários/uso terapêuticoRESUMO
Three impression tray adhesives were tested for their antimicrobial actions on three bacteria strains used for disinfectant studies. The colony forming unit (CFU) counts from plating the adhesive-exposed bacteria showed a significant reduction in number compared with the CFU of the controls. Statistical analyses confirmed the significant reduction (p < 0.05) for all but one test case. Proper infection control procedures should always be followed, but the added benefits of disinfection by impression tray adhesives can help prevent cross contamination.