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. Last Updated: 07/27/2016

Decoded DNA to Aid Cholera Fight




The genome of the bacterium that causes cholera has been decoded, paving the way for devising better vaccines and drugs against a major killer, which has caused seven pandemics since 1817.


With the genome sequenced, all of the 3,885 genes found in the bacterium's inventory are now open for inspection, giving biologists the basis for understanding every detail of the microbe's evolution and its tricks for surviving in such different conditions as the open ocean and the human gut.


The genome was sequenced by the Institute for Genomic Research in Rockville, Maryland and is described in an article published Thursday in the journal Nature.


The bacterium turns out to have 4,033,460 units of DNA, which, unlike most other known bacteria, are arranged in two chromosomes, one of them large, the other small, rather than just one. Analysis suggests that the smaller chromosome was once a so-called plasmid, a small gene-laden ring of DNA that bacteria swap back and forth among themselves. Plasmids are vehicles that allow bacteria to share properties such as drug resistance. The larger chromosome has the usual housekeeping genes, which are similar to those of E. coli, a common, harmless inhabitant of the human gut. The smaller chromosome seems to contain many of the genetic elements that make the cholera organism pathogenic.


Dr. John Mekalanos, a microbiologist at Harvard University, said he had used the cholera genome to make a gene expression chip, a device that tests when any of the bacterium's genes are active. The chip should help determine which genes are switched on when the bacterium is growing in the human intestine. Such knowledge may pinpoint ways to attack the bacterium, Mekalanos said.


The cholera bacterium belongs to the Vibrio family of microbes, which are found everywhere in the world's oceans. Most are harmless, and the expression chip may help show how Vibro cholerae, the causative agent of the disease, acquired the means to infect people.


Because its genes are central to everything the bacterium can do, "determination of the Vibrio cholerae genome sequence represents a milestone of profound significance,'' said Mekalanos.


Although cholera has been a known disease for thousands of years, it has been poorly understood for most of that time. There have been seven pandemics and for the past 40 years a cholera pandemic has persisted in Asia, Africa and Latin America.


"This organism has so far resisted many conventional eradication efforts by acquiring new genes and rapidly evolving. Distinctly different strains have caused multiple pandemics in the past and novel strains will continue to emerge," said Mekalanos. So understanding the bug's genome "will allow us to define new changes with perfect resolution and thus learn how this organism adapts and becomes a more efficient pathogen of humans.''


Mekalanos noted that existing anti-cholera vaccines have not proved effective. But he said it is clear that people infected by cholera once become immune for the rest of their lives. This shows that immune protection is possible.


It also means that "in endemic areas, it's a disease of children'' because most adults have already had cholera and are immune, said Mekalanos.


Microbiologist Rita Colwell, a cholera researcher who is director of the National Science Foundation, added that "if the disease is to be conquered, it will require a full understanding of its ecology and natural host relationships in the aquatic environment.''