Simona Seizova - Infectious Diseases and Immune Defence division

Simona Seizova - Infectious Diseases and Immune Defence division

Location: 
Davis Auditorium
Start Time: 
Wed, 30/10/2019 - 1:00pm
End Time: 
Wed, 30/10/2019 - 2:00pm

The molecular dissection of host manipulation by chronic Toxoplasma gondii

Wednesday seminar (this is a PhD confirmation seminar)​ hosted by Associate Professor Chris Tonkin

Toxoplasma gondii is an obligate intracellular parasite, which chronically infects one third of the world’s population. Toxoplasma infection severely affects immune-compromised individuals, resulting in birth defects, blindness, or brain encephalitis. Toxoplasma extensively manipulate their host cell by exporting a distinct repertoire of effector proteins. This process interferes with the host transcriptional program and is thought to enable parasite persistence and dissemination in spite of the host immune response. Eventually, Toxoplasma establishes a chronic brain infection that becomes a reservoir for disease reactivation and is seemingly drug resistant. Little is known about how this chronic stage of infection persists post-cyst formation, or whether protein export and host manipulation play a role in latency.
 
During her PhD, Simona has determined that latent Toxoplasma bradyzoite -cysts alters the host transcriptional program, distinct from acute stages, and shows that this occurs via the export of parasite proteins. Simona has identified parasite protein IST, an inhibitor of host IFNg signaling, as a bradyzoite exported protein. Furthermore, Simona has demonstrated that protein export is critical for protecting bradyzoite infected host cells from undergoing IFNg-mediated cell death, thus enabling cyst persistence. This suggests there is a role for protein export and parasite manipulation in chronic Toxoplasma infection.  Simona’s work provides the first evidence of a mechanism used by Toxoplasma bradyzoites for their long-term survival and identifies a potential drug target for the clearance of chronic toxoplasmosis.