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Comparative study reveals genes related to cholera pandemic
By Birgit Reinert


Researchers have compared different types of the bacterium Vibrio cholerae and identified genes unique to pandemic strains as well as genes that are specific to the seventh pandemic of cholera. This pandemic—which broke out in Indonesia in 1961 and has since spread to India, the mainland of Asia, West Africa, and Latin America—was initially caused by a single subtype of V. cholerae. By analyzing the genomic data of variant strains, the researchers expect to gain insights into the genetic changes that transformed this subtype into a devastating human pathogen.

Vibrio cholerae isolated from the Peru epidemic in 1992.

In the study, the researchers constructed a genomic V. cholerae microarray based on the only sequenced strain—known as El Tor O1 strain N16961—which was isolated in 1971 during the seventh pandemic in Bangladesh. They used the array to compare the gene content of this strain to that of nine other V. cholerae strains. These other strains, which included pathogenic and nonpathogenic strains, came from different cholera outbreaks around the world over decades of time.

To the researchers' surprise, the difference between the genes of the sequenced strain and those of the other strains is only about one percent. Genes unique to the seventh pandemic strain were found in two chromosomal gene clusters. These genes may encode some of the key properties responsible for the strain's effectiveness as an agent of pandemic cholera.

"The evolutionary success of the seventh pandemic clone of V. cholerae as an endemic and pandemic pathogen may be more related to its improved interaction with the human host than to its improved fitness within environmental reservoirs," the researchers write in Proceedings of the National Academy of Sciences. The findings were published by John J. Mekalanos, of Harvard Medical School in Boston, Massachusetts, and colleagues in collaboration with researchers at The Institute for Genomic Research (TIGR) in Rockville, Maryland.

Knowledge about the virulence genes may help prevent the disease from spreading into previously cholera-free locations. "Now that we have identified a number of unique genes that define the seventh pandemic clone, it will be possible to delete these genes systematically to address their potential roles in human infection and in promoting fitness of V. cholerae in environmental ecosystems," the researchers conclude.

Vibrio cholerae is responsible for seven cholera pandemics around the world and millions of deaths throughout the centuries. Cholera can be mild or even without symptoms, but severe infections cause extreme diarrhea and dehydration and can lead to death unless treated immediately. The name Vibrio derives from the Latin because the rod-shaped bacterium possesses a single polar flagellum and appears 'to vibrate'.

Some members of the research team had collaborated previously on the genome sequence of Vibrio cholerae El Tor N16961, which was published in 2000. Data on this pandemic strain can be found on the TIGR website.

See related GNN article
»Cholera genome sequenced

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Dziejman, M. et al. Comparative genomic analysis of Vibrio cholerae: Genes that correlate with cholera endemic and pandemic disease. Proc Natl Acad Sci USA 99, 1556-1561 (February 5, 2002).

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