Toxoplasma gondii Flashcards
(38 cards)
What do T. gondii infect?
Any nucleated cell in warm-blooded animals, with cats as the definitive host (only host that sheds oocytsts)
How dangerous is T. gondii?
It is asymptomatic in cats and most humans.
It can become dangerous in immunocompromised humans and during pregnancy
How fast can T. gondii enter a cell?
In 10-30 seconds (rapid)
What are the key features of T. gondii that allow for rapid entry?
- Actin-based gliding motility
- Adhesins
- Apical complex
What is actin-based motility gliding?
The mechanical power that allows T. gondii to enter cells (movement mechanism).
It is powered by myosinA pulling on acting filaments that are connected to surface adhesins
What are adhesins?
Adhesins like SAGs (surface antigens) and micronemal proteins (MICs) that bind to host receptors
What makes up the apical complex?
Specialised organelles including:
- Micronemes (which release adhesins)
- Rhoptries (form the moving junction and parasitophorous vacuole)
- Dense granules (modify vacuole post-invasion)
What is the sequence of cellular invasion by T. gondii?
- Initial contact via SAGs
- Apical reorientation and MIC redeployment
- Moving junction formation using rhoptry proteins (RONs)
- Rhoptry discharge and PV formation
- Adhesion shedding and sealing of PV
- Nutrient scavenging and replication within the PV
What are the key features of the parasitophorous vacuole?
- Non fusogenic: evades host lysosomes
- Connects to host ER and mitochondria for nutrient uptake (e.g. sugars & AAs)
- Essential for immune evasion & intracellular survival
What is the process of immune evasion by T. gondii?
- Host expressed immunity-related GTPases (IRGs) to destroy PV
- T. gondii counters this with rhoptry kinase ROP18 which deactivates IRGs
- T. gondii also suppresses IFN-γ and IL-12 pathways to delay adaptive response.
In what strain is ROP18 kinase particularly potent?
Type I strains
What is the global prevalence of T. gondii?
50-80%, though for most it is asymptomatic
When does T. gondii shed oocysts?
They shed millions of oocysts in cat faeces- this occurs only once in life, over 1-2 weeks
What are the 3 main transmission routes for T. gondii?
- Ingestion of oocysts (e.g. contaminated soil/vegetables)
- Consumption of bradyzoites in undercooked meats
- Vertical transmission during pregnancy
What are the two stages of T. gondii?
Tachyzoites and bradyzoites
What are the features of tachyzoites?
- Rapidly dividing, acute stage that disseminates through the host
What are the features of bradyzoites?
- Slow-growing cyst form in tissues
What are the triggers for transformation between each stage?
Tachy -> Brady = Host stress
Brady -> Tachy = When immune system is suppressed
What can T. gondii infection develop into?
Central nervous system infection
What is the diagnosis for acute toxoplasmosis?
- Serology (IgM/IgG ELISA)
- PCR (detects parasite in blood)
What is the diagnosis for CNS infection?
- MRI/CT can look for brain cysts
- PCR can test for parasite in spinal fluid
What is the treatment for acute infections?
Pyrimethamine + Sulphadiazine + Leucovorin
How does that anti-parasitic drug combo work?
Pyrimethamine and sulphadiazine work to starve the parasite of folate, halting DNA production + replication.
Leucovorin acts as a rescue drug for humans, providing folate to protect human cells from folate deficiency
What forms of T. gondii do anti-parasitic drugs work for?
Only tachyzoites.
Bradyzoites are not killed by current drugs, meaning there is no cure for chronic (latent) infection
