Scientists crack genetic code for cholera microbe

One of the deadliest scourges in history has been unmasked by scientists who will announce today that they have deciphered the entire genetic code of the cholera microbe.

One of the deadliest scourges in history has been unmasked by scientists who will announce today that they have deciphered the entire genetic code of the cholera microbe.

The full genetic sequence of Vibrio cholerae, the bacterium responsible for the devastating intestinal infection, is expected to revolutionise attempts to develop better vaccines and drugs. Scientists from the Institute for Genomic Research in Rockville, Maryland, the University of Maryland and the Harvard Medical School co-operated to unravel the four million "letters" of the bacterium's two circular chromosomes. The results are published in the journal Nature.

The team includes Rita Colwell, director of America's National Science Foundation, a veteran researcher and the first person to suggest cholera bacteria can lurk harmlessly in seawater between epidemics.

Professor Colwell said that knowing the genome had already confirmed her theory about how the bacteria live naturally in close association with the microscopic animals that live in marine plankton.

The cholera genome, containing about 3,900 genes, also contains a gene for making an enzyme that breaks down the outer skeleton of zooplankton, suggesting these organisms could be its natural host. Professor Colwell said: "We've confirmed cholera has two chromosomes and each contains genes necessary formetabolism, so that if one chromosome is lost, the bacterium does not grow. We need to know what is the function of these genes in the natural environment of cholera. My theory is that humans are an unnatural host."

Cholera outbreaks occur when drinking water is contaminated with human faeces but Professor Colwell believes epidemics can be linked to rising sea temperatures and a warmer climate.

Knowing the function of the cholera genes will shed light on the natural life cycle of the microbe and could lead to better ways of predicting the environmental conditions most favourable for a new outbreak. The knowledge could also be used to produce vaccines based on a more precise knowledge of the components of the bacterium. John Heidelberg, lead author of the study, said: "The great hope is that it will enable us to find new vaccine candidates and new drugs."

Knowing the purpose of individual cholera genes should enable scientists to interfere with their normal function, perhaps by switching a gene off altogether, he said.

The research has shown that the cholera microbe acquired its lethal nature as a result of combining with a virus at some point in its history. The union resulted in the production of a deadly toxin. When cholera bacteria are ingested with contaminated drinking water, it is the action of the toxin on the walls of the small intestine that causes the severe diarrhoea, with up to four gallons of fluid being lost in 24 hours, eventually resulting in death from severe dehydration.

The scientists found most of the recognisable genes occur on cholera's larger chromosome, with the smaller chromosome possessing a "gene capture" system that may have been involved in transforming the cholera bacteria from a harmless organism into a deadly human pathogen.