|Escherichia coli (E. coli)|
Scientists have just completed sequencing the genome of Escherichia coli 0157:H7, the bacteria that can cause bloody diarrhea, sometimes with fatal consequences. Their results are being published today in the journal Nature.
By comparing it with strains of E. coli that arent harmful, they hope to target the genes responsible for the havoc it wreaks so they can find ways not just to treat disease, but perhaps even to prevent it.
Pieces of a puzzle
E. coli 0157:H7 was first identified in 1982 after an outbreak of severe bloody diarrhea that was traced to contaminated hamburger. The Centers for Disease Control and Prevention estimates that it causes about 73,000 cases of diarrhea each year, ranging from mild to severe. At its worst, the disease can progress to hemolytic uremic syndrome, a potentially fatal disease that causes kidney failure.
Although this particular type of E. coli is toxic, not all strains, of which there are thousands, are harmful. The E. coli normally found in our intestinal tracts is actually beneficial because it keeps harmful bacteria in check and synthesizes vitamins. So what is it about 0157:H7 that causes it to make us sick?
Thats exactly what scientists at the Genome Center at the University of Wisconsin wanted to find out, and they hope that the sequencing of the genome will give them the answer. In 1997, they sequenced the genome for E. coli K-12, which doesnt cause human disease. "What we are interested in is trying to use a comparison between the two genomes to learn something about how these two E. coli interact with a human and why they have such very different effects on human biology," says Nicole Perna, associate professor of Animal Health and Biomedical Sciences at the University of Wisconsin, who worked on both genomes.
|This sequence zooms in on the map of the genome for E. coli 0157:H7. To get a sense of how large a project this was, keep in mind that even the most distant frame of the sequence is just a small fraction of the entire map.|
In sequencing the toxic E. col i 0157:H7, researchers found about 1300 genes that werent found in the non-pathogenic K-12 variety. "When we compared the two E. coli genomes we find large tracks where they are very, very similar," says Perna. "But intergressed and interdigitated between those shared areas are genes that are unique to one E. coli or the other, so weve defined a whole set of genes which differentiate the two organisms."
Perna and her colleagues used an approach called whole genome random shotgun sequencing to translate the bacterias genome, a process which took three years. "The basic idea there is that we fragment the genome into tiny randomly defined pieces and then we sequence each of those little pieces and we keep sequencing the fragments until we cover the whole genome about six times over," explains Perna. "Then we assemble all of those fragments into one complete chromosome."
What we know isnt enough
It will take a while to gain new insights from the genome, but scientists do already know the mechanism by which pathogenic E. coli does damage. Receptors on the bacteriums surface help make it stick to cells in the intestine almost like a space ship docking, says Frederick Blattner, director of the Genome Center. Through these receptors, E. coli injects proteins into the intestinal cells. "When the proteins on the inside hook up to the membrane, they reach back and grab the bacteria and pull it really tightly and then get it closely opposed to the intestinal cell walls," he explains. "Then it starts secreting more proteins and starts doing damage to the cells on the intestinal lining and thats where the bleeding comes from."
|Testing meat for microbial contamination|
Pathogenic E. coli are also somehow able to protect themselves against the acids found in the intestine, and they secrete a toxin called shiga toxin, which gets into the bloodstream and damages blood vessels and organs.
The next step
"One of the things that comes out of this study very explosively is that there are maybe hundreds of genes that maybe have to act in sequence and in concert before you can get the full effect," says Blattner.
By identifying these genes and understanding how they work together, scientists hope to be able to find ways to treat E. coli infection. Right now there are no effective treatments, other than trying to control the symptoms.
But they also want to pinpoint ways to identify the bacterium. "In no way would food contaminated with E. coli look different, taste different, smell different," says Dr. Howard Trachtman , director of pediatric nephrology at Schneider Childrens Hospital. In addition, it doesnt take a lot of the bacteria to make you sick. "Its been estimated that as few as a hundred bacteria can start E. coli 0157:H7 infection, so that makes it all the more important that methods we use for surveillance are highly sensitive," says Perna.
Perna and her colleagues plan to sequence the genome of different bacteria, including other disease-causing E. coli, to put together a complete picture of all the possible genes that could be harmful. "We hope by comparing all of these genomes to each other we can learn more than we could by studying any one of them individually," she says.
Blattner hopes that mapping these genomes will one day lead to DNA chips that will quickly and efficiently identify not just E. coli, but other dangerous microbes, before they hit the food supply. "You might be able to envisage in the future a little unit that you put a little bacteria in there and within minutes you get a printout that says plague, salmonella, 0157, something youve never seen before but looks dangerous," he says. "So I think that we are looking at the possibility of some marvelous new kinds of tests."
In the meantime, consumers will have to rely on safe food handling procedures to try and contain E. coli outbreaks.