WASHINGTON (Reuters) - Scientists say they have sequenced the genome of the bacteria that causes cholera -- one of the most ancient and deadly causes of disease known to humankind.
Sequencing is a first step toward mapping out all the genes in an organism. The scientists hope they can use this information to develop better vaccines and treatment for cholera, which killed nearly 8,500 people last year and sickened 223,000, according to the U.N.'s World Health Organization.
Writing in the science journal Nature, the researchers, led by a team at the Maryland-based Institute for Genomic Research (TIGR), said they hope to understand how bacteria that usually live free in estuaries, rivers and lakes came to infect human beings, and with such deadly effects.
``Determining the genomic sequence of medically important pathogens such as Vibrio cholerae holds enormous promise for helping us fight some of the world's most intractable infectious diseases,'' Dr. Anthony Fauci, director of the U.S. National Institute of Allergy and Infectious Diseases (NIAID), which funded the project, said in a statement.
``Besides contributing to our understanding of how a microbe causes disease and survives in the environment, sequencing studies enable scientists to locate genes that may lead to potential new targets for vaccine candidates, drugs and diagnostic tools,'' Fauci added.
The researchers said they already had discovered some interesting things about cholera, which kills by causing severe diarrhea that drains the body of fluids and salts.
To their surprise, they found that the Vibrio cholera bacteria has nearly twice as much genetic material as they thought it would contain. And, unusually for a microbe, it is arranged on two circular chromosomes instead of one, which suggests it has swapped a lot of genetic material with other bacteria.
``It looks like it has been acquiring genes for a long time,'' John Heidelberg of the Institute for Genomic Research told a news conference.
Microbiologist John Mekalanos of Harvard Medical School, who also worked on the paper, said his team had already learned some things valuable for producing a cholera vaccine.
Scientists knew that cholera toxin produced by the bacteria was the main cause of the diarrhea. They removed that protein from attenuated or weakened forms of the bacteria used to make vaccines, but these vaccines still can cause intestinal upset.
New, Toxic Protein Identified
As part of the genome project, another protein has been identified. Called RTX, it is a huge protein, more than 10 times bigger than the average protein. It disrupts the endothelial cells that line the intestine, causing inflammation.
``Now we can remove this protein from vaccines,'' Mekalanos said.
He said the team plans to make a DNA chip -- the biological equivalent of a computer chip -- that will contain all the genes of V. cholerae. They can use this to compare its genes to the genes of other microbes to see which ones are similar.
They also can use such a chip to study which genes become active when the bacterium is starved, when it is in a human host, when it is dormant, and which ones it uses to grow.
``We don't know all there is to be known about making a good vaccine against cholera,'' Mekalanos said.
Dennis Lang, an expert on bacterial diseases at NIAID, said the project also may have explained why the cholera bacteria can go into a spore-like state in which they are alive but cannot be cultured. This makes them hard to detect in water.
``The authors of the Nature paper found some genes in the cholera genome that appear to be related to genes from sporulating bacteria,'' he said.
``What role these cholera genes may play in that quiescent state, if it exists, remains to be seen, but this information will provide much fodder for that research.''
Scientists know that bacteria often swap genes, and that this habit can turn deadly a harmless bacteria such as E. coli, like the O157 strain that causes food poisoning.
Mekalanos said cholera, already hard to control with antibiotics, could become even harder to manage.
``There is always the potential that cholera will change dramatically in some way that will make it capable of withstanding our efforts,'' he said.
He noted there already was some evidence that one strain had evolved resistance to the chlorine treatment of water.