Trypanosomes and renal insufficiency

Trypanosomes and renal insufficiency
Trypa

The African trypanosome Trypanosoma brucei is a blood parasite capable of infecting many mammals. Humans are provided with natural immunity against infection through the activity of the protein apolipoprotein L1 (APOL1): captured via endocytosis, APOL1 forms pores in the lysosomal membrane, leading to the death of the trypanosome.

In a publication in the scientific journal Nature Communications, Prof Etienne Pays and his team from the ULB's Laboratory of Molecular Parasitology (Faculty of Science) sheds further light on the way human APOL1 kills the parasite. APOL1 does not just induce lysosomal membrane permeabilization. Once it has accomplished this, it is transported to the mitochondrion where it again induces membrane permeabilization. The subsequent release of a mitochondrial endonuclease into the nucleus leads to trypanolysis.

However, this defence mechanism is not infallible: two trypanosomes, Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense manage to evade APOL1, and can infect humans with sleeping sickness. Two distinct mutations of APOL1 enable a number of West African populations to be immune to one of these trypanosomes. However, in 2010, Etienne Pays' laboratory proved that this evolutionary advantage went hand in hand with an increased risk of renal insufficiency.

While the mechanism allowing these mutations of APOL1 to trigger renal pathology remains completely unknown, our new observations on the biology of APOL1 allow us to imagine how the disease could occur in and to develop new research hypotheses.


Explore further

Rapid testing for gene variants in kidney donors may optimize transplant outcomes

More information: "Coupling of lysosomal and mitochondrial membrane permeabilization in trypanolysis by APOL1." Nature Communications 6, Article number: 8078 DOI: 10.1038/ncomms9078
Journal information: Nature Communications

Citation: Trypanosomes and renal insufficiency (2015, August 27) retrieved 29 January 2020 from https://medicalxpress.com/news/2015-08-trypanosomes-renal-insufficiency.html
This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no part may be reproduced without the written permission. The content is provided for information purposes only.
39 shares

Feedback to editors

User comments