©2019 by Michael Clarke-Whittet, all views expressed here are my own.

Michael Clarke-Whittet

PhD student in quantum biology tackling molecular noise and quantum decoherence.
I like playing music, hiking, and the rule of three in lists.

  • Michael Clarke-Whittet

African Trypanosomiasis part 1: The sleeping sickness that always wins

I worked with trypanosomes in Dundee during my master’s degree. Trypanosomes are single celled organisms that can cause a range of infectious diseases, such as African sleeping sickness. In this case the bloodsucking tsetse fly bites somebody, and transfers the single-celled trypanosomes in its saliva into the bloodstream, similar to how malaria is transmitted. From the bloodstream, the trypanosomes eventually make their way into the spinal cord and the brain stem, feeding off the tissue there and secreting the sleep-inducing drug tryptophol until the sufferer falls unconscious. This disease is almost always fatal and is accompanied by malnutrition and dehydration as the sufferer is not able to sustain themselves.

The human immune system can detect the trypanosomes in the blood, as they have a ‘coat’ of sugars and proteins that are distinct from the host. So how do trypanosomes survive when the immune system can see them and mount a defence? It’s all about timing: when trypanosomes are destroyed by the natural immune system the survivors begin to change their coats(1). They switch sugary protein A to sugary protein B because the immune system doesn’t recognise the B-type trypanosomes. Of course this triggers another immune response, but the response to coat A and coat B don’t overlap; they are look like entirely different organisms.

Coat-switching over time: The abundance of unique trypanosome coat types (A, B, C, D) changes in response to detection by the host immune system

So each time the host begins to kill the invading trypanosomes the trypanosomes put on a new disguise. How many times can they do this? One report suggests they could do this around a thousand times based on the number of genes they have devoted to this(2). Remarkably, they can generate even more diversity by creating ‘mosaic’ genes on the move, combining one gene with another to make a unique new gene as needed – an astonishing feat of rapid, temporary, adaptation. This means that trypanosomes can survive this detection-disguise cycle far beyond the average survival of the host.

The underlying genetic system that can support this tremendous repertoire of possible coats is large and sophisticated. The tactic of coat-switching is only possible with tight control – wearing only one coat at time means that only one immunity can develop at a time. Trypanosomes that present too many signals to the host immune system give away too much information – they must absolutely silence all the inactive coat genes. This is quite difficult, and is generally achieved by the unusual trait of self gene-editing; a risky business for a living organism. There is one complete gene where the code for the active coat is kept and transcribed; the other genes are all incomplete. When the active gene is no longer useful, an inactive gene is swapped into the active slot – like changing DVDs in a DVD player. This is achieved in a variety of ways that is astonishing in its own right.

While I was writing up my thesis I researched the epidemiology, how a disease spreads geographically, to connect my work in this system with the real importance of the infections, which primarily affects sub-Saharan central Africa. I learned that in the past hundred years Africa has seen the greatest outbreaks of trypanosome infection known killing 2/3 people in affected areas in Uganda in just one year, only decreasing again with the invention of a couple drugs that can provide relief. Why would this be? The answer may not, in fact, be molecular but sociological.

1. Mcculloch R, Cobbold CA, Figueiredo L, Jackson A, Morrison LJ, Mugnier MR, et al. Emerging challenges in understanding trypanosome antigenic variation. 2017 https://doi.org/10.1042/ETLS20170104

2. Taylor JE, Rudenko G. Switching trypanosome coats: what’s in the wardrobe? Trends Genet. 2006 Nov 1;22(11):614–20.


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