J-E.coli and Hyde
By Paul Dean
Institute of Cell and Molecular Biosciences, University of Newcastle-upon-Tyne
For most non-scientists, the term E. coli conjures up images of undercooked hamburgers or diarrhoea. However, ask a typical biologist and the image of E. coli could not be more different.
This bacterium is used in laboratories the world over as an invaluable biological tool to study genes and to produce almost any chosen protein. E. coli is ideal for this role because its biology is relatively simple, it grows very quickly, is easy to keep and is in fact nearly always harmless.
Despite its infamous public image, E. coli is generally a ‘good’ bacterium found within our digestive tract where it causes no problems at all and may even be beneficial. Remarkably, this amiable little bug, like many other bacteria, can pick up ‘bad’ pieces of DNA from the environment, turning it from a passive, commensal bug into a potentially serious killer. Just a few simple transactions of DNA, combined with a several million
years of evolution and E. coli has become a feared infectious agent, capable of killing up to a million people each year, particularly young infants in developing countries.
So what makes E. coli so deadly? A virulent form of E. coli (also known as EPEC) has recently had almost every one of its genes identified by the Sanger Institute in Cambridge, giving us a massive advantage in searching for the bacterial genes that cause disease and diarrhoea. Over the past few years, research has shown that at some point in its evolution, friendly E. coli acquired a piece of DNA that gave it the ability to physically ‘inject’ its own proteins and toxins into the cells of our digestive tract. The bacterium actually possesses a molecular ‘syringe’ on its surface (which is even shaped like a syringe too). Inside our gut cells, the injected bacterial proteins do a huge variety of things and manipulate the cell for the needs of the bacterium - in the process our cells get sick, cannot function normally, and the result is diarrhoea. What advantage this gives to the bacteria remains unclear. Amazingly, the importance of the acquired DNA can be demonstrated in the lab simply by putting it into harmless E. coli, which gives it the ability to then inject proteins into our cells. The injected proteins are the workhorses of the disease process.
“E. coli has become a feared infectious agent” |
While E. coli sits happily on the surface of our gut, its injected proteins are busy interacting, interfering, disrupting and subverting many cellular processes. In particular, a number of the proteins injected by E. coli interfere with the way gut cells contact one another. Normally, cells in the intestine are very tightly joined to each other by closed ‘junctions’, creating a barrier to the passage of water and stopping it simply leaking out from the body. By opening these junctions, the E. coli proteins disrupt this cell-made barrier, allowing water to pass which contributes to what we know as diarrhoea. Even more interesting is the fact that the bacteria neatly controls the activity of the injected proteins, only allowing them to act at set times after injection. This activity is directed by yet another bacterial protein on the surface of E. coli that never even enters the intestine cell. So, from its ringside seat on the surface of the intestine cell, E. coli appears to be telling its protein what needs to be done - and the unfortunate outcome is diarrhoea.
Other bacteria that cause disease including Salmonella, Shigella and Yersinia (which was responsible for the plague) also possess many injected proteins which are highly similar to those of E. coli i.e. bacterial pathogens seem to be very good at sharing their disease-causing proteins. Therefore, understanding how the normally harmless E. coli can cause disease gives us many vital clues into how other bacteria may cause disease and, maybe more importantly, it also provides us with knowledge about how our own cells work. For example, little is known about the mechanisms behind how our cellular ‘junctions’ are regulated within our intestine, i.e. what keeps them tight shut. E. coli employs at least five different proteins to open the junctions, providing us with invaluable tools to dissect clearer the mechanisms by which our junctions function. In terms of therapeutic potential, the advantages are obvious. As E. coli is able to open up the
junctions to cause diarrhoea, then by understanding how it does it, we may be in a position to close them back up, possibly slowing down disease. Moreover, knowing which injected proteins are the most important in disease provides targets for use in immunisation programmes, particularly for vulnerable people in infected areas.
“While E. coli sits happily on our gut, its proteins are busy disrupting many cellular processes”
So, from a simple, normally harmless bacterium that exists by the millions in each and every human gut, we are able to learn a huge amount about how bacteria cause disease and also how our own cells function. Until recently only five injected EPEC proteins were known. In 2004 alone, over twenty potential injected proteins have been identified. Clearly, we have only reached the tip of the iceberg in discovering how the E. coli cause diarrhoea but the potential advantages and knowledge gained ensure that this nasty form of this bacterium may be extremely beneficial after all!
This article first appeared in the University of Bristol Re:search magazine and is reproduced with permission. See http://eis.bris.ac.uk/~pslsw/ for more information.
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