Download PUTTING SLEEPING SICKNESS TO BED

PUTTING SLEEPING SICKNESS TO BED
Dr Derek Nolan
African trypanosomes cause sleeping sickness, a devastating and fatal illness in humans and
livestock, throughout many parts of sub-Saharan Africa where the tsetse fly vector is found. The
most common form of the disease in humans is caused by Trypanosome brucei gambiense , (T. b.
gambiense), which can evade the innate defence normally provided by human apolipoprotein L1
(APOL1), a toxin that kills most trypanosomes. This toxin is taken up from the human bloodstream by
trypanosomes during their normal feeding processes but once internalized APOL1 inserts itself into
the membrane of their digestive system, disrupting them and thereby killing the parasite.
A paper published in Nature this week by a consortium of European researchers including Dr Derek
Nolan, PI of the molecular parasitology group in the School of Biochemistry and Immunology, has
now finally revealed how these parasites have overcome this defence.
Dr Nolan and his colleagues have shown that T. b. gambiense has evolved three strategies to escape
destruction by APOL1. First, the parasite makes a novel protein that actually stiffens their
membranes and prevents insertion of APOL1. However, two additional features are necessary to
secure the defence against APOL1: decreased internalization of the toxin through a modification of
the receptor for uptake combined with an alteration of the acidity of the digestive organelles to
ensure a more rapid digestion of internalized APOL1. This study demonstrates once again the
ingenuity of these parasites in responding to their host but also provides a new opportunity to
develop treatments for the highly infectious T. b. gambiense.
In a report on the publication of the paper BBC News quoted Dr Wendy Gibson, professor of
protozoology at the University of Bristol, ‘They’ve finally solved the mystery of how gambiense has
been fighting our defences. It is a meticulous piece of work.
http://www.bbc.co.uk/news/health-23755038
http://www.ncbi.nlm.nih.gov/pubmed/23965626
Uzureau P, Uzureau S, Lecordier L, Fontaine F, Tebabi P, Homblé F, Grélard A, Zhendre V, Nolan DP, Lins L, Crowet JM, Pays
A, Felu C, Poelvoorde P, Vanhollebeke B, Moestrup SK, Lyngsø J, Pedersen JS, Mottram JC, Dufourc EJ, Pérez-Morga D, Pays
E. (2013) Mechanism of Trypanosoma brucei gambiense resistance to human serum. Nature. 2013 Aug 21. doi:
10.1038/nature12516. [Epub ahead of print]