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MICROBIOLOGY
Unique Genes Found in 7th Pandemic Cholera Strain
Researchers have identified 22 genes in a particularly nasty strain of cholera bacteria that may eventually explain how it has evicted classic varieties from Asia and established the deadly diarrheal disease in Africa and Latin America.
Using the completed Vibrio cholerae genome, researchers in the lab of John Mekalanos identified groups of genes that may eventually reveal how the bug becomes a global health threat. Photo by Graham Ramsay
Using the powerful postgenomic tool of microarray technology, the study also helped to define genes unique to other strains responsible for most local outbreaks and previous global pandemics of cholera. The results were published in the Feb. 5
Proceedings of the National Academy of Sciences.
Scientists want to discover and disable the secret of El Tor's success in the seventh pandemic, which began in 1961 and continues today. Like other bacteria, Vibrio cholerae is notoriously promiscuous with its genes, swapping base pairs after not much more than a wink and a nudge. Not all Vibrio cholerae strains cause disease. The virulence of the pathogenic strains comes from the bacteria's easy acceptance of two pieces of foreign DNA, one a virus carrying the cholera toxin gene and another segment that enables the organism to adhere to the intestinal wall.
Microarray results. Compared to the El Tor N16961 cholera strain (bottom row), researchers found only about a 1 percent difference in genes among nine strains of vibrio cholerae, including two El Tor strains that did not become pandemic (NCTC 8457, MAK 757), an infectious El Tor strain that does not cause disease (2740-80), three strains of classic cholera from the sixth pandemic (569B, O395, NIH 41), two strains of seventh pandemic El Tor (HK1, C6709), and the closely watched 0139 El Tor strain (MO10) that emerged in 1992 in South Asia and that some people believe may herald an eighth pandemic. Courtesy of Michelle Dziejman and PNAS
Two years ago, a definitive version of the dominant El Tor cholera genome sequence was completed by The Institute for Genomic Research in Washington D.C. (better known as TIGR) and a group of researchers including John Mekalanos, the Higgins professor of microbiology and molecular genetics and chair of that department, who is a senior author of the latest study.
Using the 3,890 genes in the sequenced El Tor strain N16961, HMS research associate Michelle Dziejman, technician Emmy Balon, and their colleagues assembled a microarray from scratch. Strain by strain, they compared genes from nine other distinct strains. The one-sided microarray identification only finds genes the test strains lack in comparison to the sequenced El Tor strain.
Most of the 22 genes unique to the seventh pandemic are clustered in two islands on the larger of Vibrio's two chromosomes, suggesting horizontal transfer from another organism. The researchers plan a battery of tests, including creating knockout versions of the cholera bacteria to determine the function of these genes.
"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 paper concludes.
--Carol Cruzan Morton
Copyright 2002 by the President and Fellows of Harvard College
