Trypanosomatids

Question 1

What are two special biochemical processes possessed by T.brucei?

Answer 1

T.brucei has two special organelles, kinetoplast and glycosomes, which have have biochemical processes that could make for good drug targets

The kinetoplast contains the mitochondrial genome (maxi and mini circles). Here takes place RNA editing where enzymes ligase RNA pieces which could make for a good drug target.

Trypansomatids depend on glucose/glycolysis for energy. They have glycosomes, membrane-bound organelles absent in humans, in which enzymes for glycolysis are found like aldolase. The enzymes for glycolysis that consume ATP are not regulated but the membrane protects the parasite from a toxic glycolysis cascade that would burn through all the ATP from the cytosol. Targeting proteins important into the glycosome, like inhibiting PEX5 (ligand) and PEX14 (receptor), could be good drug targets to render glucose toxic to the cell and unable to process it.

Question 2

What are the 3 “syndromes” caused by Leishmania species?

Answer 2

1. Cutaneous leishmaniasis: self healing lesion
2. Mucocutaneous leishmaniasis: infection of oral and nasal mucosa, disfiguring
3. Viscera leishmaniasis: infection of liver, spleen and bone marrow. Lethal if untreated-

Which syndrome is dependent on species and host immune status.

Question 3

Explain what transsialidase does for T. cruzi and why this is not real antigenic variation.

Answer 3

Mammalian host cells have sialic acid on them. T. cruzi uses its enzyme transsialidase to “steal” this sugar from the host and decorate itself as a form of immune evasion mechanism. This is not considered real antigenic variation once there is not a gene family of which only one variant is expressed.

Question 4

How to trypanosomatids evade the immune system?

Answer 4

Trypanosoma brucei has antigenic variation, the VSG coat changes every few generations. T. cruzi can decorate itself with host sialic acid with the help of transsialidase.