To gain a foothold in the gut, the O157 strain of E coli conducts a chemical “conversation” with human cells, injecting bacterial proteins into the cells through a molecular syringe.
Until recently, it was thought that this conversation involved only a handful of proteins. However, a team of researchers at the University of Birmingham, in collaboration with scientists in London and Japan, have identified more than three-dozen proteins that can pass through the molecular syringe and enter human cells. These proteins are thought to help the bacterium create an environment in which it can flourish.
The O157 strain of E. coli is commonly in the news because of its propensity to cause outbreaks of severe food poisoning or to infect young children after farm visits. In 2005 an outbreak affected more than 150 school children in Wales and the bacteria was also blamed in July this year for infecting 14 people in Leeds.
The bacteria release a toxin, known as vero-toxin or Shiga toxin, into the body. This can cause severe gastroenteritis. In a small number of cases, particularly in the elderly or young, it can also trigger renal failure, brain damage or even death.
Initially, the team at Birmingham, headed by Professor Mark Pallen, used computers to identify 49 candidate genes from E. coli O157 that were capable of making proteins that might interact with human cells. Laboratory analyses confirmed that at least 39 of these proteins were able to enter human cells through the molecular syringe and are thus likely to help the bacterium manipulate human cells to its own benefit.
Professor Pallen explains: “One of the key tasks we face in developing new approaches to preventing and treating E. coli O157 infections is understanding how the bacteria become established in the bowel and survive in the body long enough to release the vero-toxin, which causes the severest symptoms. We examined the dialogue that takes place between the bacteria and the body. We discovered that this is a much more complex process than previously thought. We have identified more than 30 proteins that the bacterium injects into cells, before or alongside the release of the vero-toxins. We believe that these proteins are involved in a number of complex functions including helping the bacteria adhere to the gut wall, making the lining of the intestine more leaky and toning down the body’s immune response.”
These findings have been reported in a paper published in the Proceedings of the National Academy of Science. The research also showed that many of the injected proteins originate from viruses that have infected the bacteria.
Professor Pallen continues: “The bacterium injects the cell with proteins to create an environment in which it can flourish. Curiously, to infect us, the bacteria rely on components of viruses that have in turn infected them - a strange molecular example of poacher-turned-gamekeeper. In fact, it now appears that bacterial viruses have been a major driving force in the evolution of virulence in this bacterium. We are now taking the research forward by trying to identify the exact function of each protein individually, in the hope of gaining a better understanding of the process of infection in its entirety.”
For more information contact Ben Hill, University of Birmingham Press Officer, telephone 0121 414 5134 or 07789 921163.
NOTES TO EDITORS
The paper: “An extensive repertoire of type III secretion effectors in Escherichia coli O157 and the role of lamboid phages in their dissemination” is published in the Proceedings of the National Academy of Sciences
Escherichia coli (usually abbreviated to E. coli) is a bacterium that lives in the intestines of humans and other animals and is a common laboratory model organism. Some strains of this bacterium, such as E. coli O157, cause life-threatening infections.