Lecture 7 Trypanosoma brucei

Question 1

what type of trypanosomatid is trypanosoma Brucei?

Answer 1

A salivarian

Question 2

what disease does T. brucei cause?

Answer 2

Causes a disease called nagana

Question 3

T. b. rhodesiense

Answer 3

-causes the more virulent, East African or Rhodesian, form of African sleeping
sickness and is usually transmitted by Glossina morsitans.
* Wild game and domestic animals may serve as reservoir hosts and sources of human infection.
* The disease runs its course so rapidly (2-6 months) in humans that person-to-person
transmission via the tsetse fly is uncommon.

Question 4

T.b. gambiense

Answer 4

-causes West African, Equatorial African, or Gambian sleeping sickness, a more
chronic form of the disease. Domestic and wild animals, such as pigs, antelopes, buffaloes, and
reed bucks, may serve as reservoir hosts.
* The insect vectors are Glossina palpalis and G. tachinoides.
* Human-to-human transmission via the bite of the tsetse fly is common since the trypomastigotes
can remain in circulating blood for 2 to 4 years.

Question 5

How do humans defend against T. Brucei?

Answer 5

–trypanolytic protein apolipoprotein-L1 (APOL1) found within two serum protein complexes,
trypanosome lytic factor 1 and 2 (TLF-1 and TLF-2).

Question 6

Can humans get infected by T. Brucei gambiense and and T. brucei rhodesiense?

Answer 6

-Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense have evolved specific mechanisms to overcome this innate resistance

Question 7

T. brucei serum resistance

Answer 7

TLF1 and TLF2 are taken up by the parasites and deliver lytic APOL1 protein to the lysozyme. A conformational change on the low pH environment of the lysosome releases APOL1 and exposes domains that allow it to form anionic pores in the membrane, leading to osmotic imbalance and cell lysis.

Question 8

How is T. brucei Rhodesiense resistant to the TLF1-2?

Answer 8

• In T. b. rhodesiense, expression of the SRA (Serum Resistance Antigen) gene, a
  truncated VSG, confers resistance to lysis by both TLF-1 and 2.
• Deletion of the VSG surface loops results, in its trafficking through the endocytic
  pathway, where it is able to bind APOL1 and prevent pore-forming activity in the
  lysosome.

Question 9

How is T. brucei gambiense resistant to the TLF1-2?

Answer 9

• T. b. gambiense has evolved a complex, multi-component mechanism of human
  serum resistance involving:
• reduction in the binding affinity of TbgHpHbR for TLF-1
• expression of a T. b. gambiense specific truncated VSG (TgsGP) which
  increases resistance of the lysosomal membrane to APOL1 disruption
• enhanced expression or activity of cysteine proteases (CP) that aid
  degradation of APOL1 within the endocytic pathway

Question 10

Salivarian trypanosome bloodstream

Answer 10

forms are covered by Variant Surface
Glycoprotein (VSG) dimers comprising 5–10 % of the total cell protein.
* The VSG molecules have molecular weights varying between 50 and 65 kDa and
completely conceal most underlying essential membrane proteins such as receptors
and transporters.
* Each VSG carries a glycosyl phosphatidylinositol anchor with two myristate chains.
* The bloodstream forms of T. brucei and T.
congolense also have a transferrin receptor;
this is built of two proteins called ESAG6 and
ESAG7 which are related to VSG.
* T. brucei stages developing in the insects
switch to expression of procyclins upon
arrival in the midgut: these are
“procyclins” with central EP or GPEET
repeats.