What the EHEC is that diagram of ?

 The history of science is peppered with great moments where people have gone above and beyond the call of duty in order to present their work in an accessible way. Think Florence Nightingale, and how she drew attention to the abominable conditions in hospitals through the use of a simple chart.  Or perhaps Vesalius, and his intricate and detailed diagrams of the human anatomy. 

The following paper deserves it's place among the greats, as it too has taken the graphical representation of science to a whole new level.

So what is this paper about?

The paper itself is about a bacterium known as Escherischia Coli, or E.coli for short. This species of bacterium lives in the digestive system of many animal species. 

Not all E.coli are the same, and there is a diverse set of different strains of this bacteria, including ones that can cause disease. The focus of this paper is on Enterohaemorraghic  E.coli serotype O157, or EHEC for short. EHEC causes bloody diarrhoea in humans, and hemolytic uremic syndrome. This is best known for regularly causing food outbreaks due to improperly cleaned meat.

It causes these diseases due to the way it attaches to cells in the large intestine. It has a set of genes, known as the LEE (Locus of Enterocyte Effacement), which causes the expression of proteins that force an attachment to the microvilli of the intestine. This attachment causes the microvilli to be severely damaged, and leads to diarrhoea.

Like many bacteria that cause disease in humans, EHEC does it because it doesn't necessarily belong in the human digestive tract. The LEE, which make it cause this disease in humans, are actually essential to its survival in it's natural host: the humble cow.

The cow's digestive system is far more complex than the human one, containing a stomach with four compartments, and a variety of different commensal bacteria to aid with digestion. Here, the EHEC's specific niche within the cow is at the reticulo-anal junction. When it gets there, it can express it's attachment genes in this area without causing the cow the slightest bit of discomfort.

In order to get there though, it has to run through the acidic compartments of the stomach. But this bacteria doesn't have any idea of when it's going to have to cope with stomach acids. Nor does it have any idea of when it reaches the recto-anal-junction. 

What it does to work these out is quite clever. The first compartment of the stomach the EHEC encounters is the rumen. This is home to lots of other bacteria, which help the cow break down the tough cellulose in grass.

These bacteria are in constant communication with eachother, using bacterial pheromones. These compounds are called Acyl-Homoserine Lactones, or AHL's for short. The rumen is choc full of them. Whilst the EHEC doesn't produce any of these chemicals itself, it can sense their presence using a regulatory gene called sdiA.

This regulatory gene tells the bacteria when it can express it's attachment proteins. 

If AHL's are present, they will filter into the EHEC, and when they bind the SdiA protein, it undergoes a transformation that allows it to do two things:

1. It will  sit on the DNA encoding the LEE, preventing it being read. This stops the attachment proteins being made.

2. It force other proteins to activate a gene called  gad,  which encodes acid resistance genes, and it will ensure that it is transcribed more. This will make the cell more resistant to acid.

So what do these two things mean?

Well, the diagram of a cow pictured below will explain:

  In the rumen, where there is lots of AHL's present, the genes encoding the LEE are repressed, whilst the genes encoding gad are upregulated. This prevents the bacteria sticking to the wrong place of the stomach, where there is high competition, and also prepares it for the environments within the acidic stomachs,
However, as it travels though the digestive system of the cow, the amount of AHLs decrease, until you get to the recto-anal junction. Here there are no AHL's, and so the LEE genes can be expressed, allowing for the bacteria to attach to this area. 


So why do I think this diagram has a place in history?
This is not just a functional representation of a cow's intestine. That could be achieved with a series of boxes drawn in microsoft word, with arrows between them. It goes beyond simple information communication, and moves towards high art. 
This is an impressionistic interpretation of a cow, but not from a human perspective. In fact, I'm not even sure it's from a bacterial perspective. It is from the prespective of the SdiA protein itself. it's most important function, within the rumen is most prominent. As the artist traces out the rest of the digestive tract, the lines become more wavy, more chaotic. Perhaps this represents how the gene itself loses a sense of itself after it passes through the acidic regions of the stomach. It only knows where it is by what isn't there, a truly confusing state of being. But when guides its bacteria to its location, a truly amazing celebration occurs, resulting in a blue plume which must represent something or other.

Sperandio, V. (2010). SdiA sensing of acyl-homoserine lactones by enterohemorrhagic E.coli (EHEC) serotype O157:H7 in the bovine rumen
Gut Microbes, 1 (6), 432-435 DOI: 10.4161/gmic.1.6.14177