Cholera's Gregarious Genes

Bacteria are legendary for their ability to swap genes for antibiotic resistance. Now researchers have evidence of how one bug at least--Vibrio cholerae, which causes cholera--may have captured other kinds of genes, including those that help make the microbe pathogenic, from other species. The findings, reported in today's Science, might also help explain unexpected similarities between the DNA of distantly related bacteria.

Integrons are strips of DNA containing repetitive nucleotide sequences that allow genes from one organism to be used by another. To date, all known integrons have been associated with genes for antibiotic resistance. But a research team led by molecular microbiologists Didier Mazel of the Pasteur Institute in Paris and Julian Davies of the University of British Columbia in Vancouver discerned that V. cholerae's integron might be capable of capturing more genes than had been thought. They first suspected this when they noted that the bug has repeated sequences that look like those in known integrons, and the sequences flank not only antibiotic resistance genes, but also genes coding for several other proteins, including some that are toxic.

To test whether the V. cholerae repeat is in fact part of an integron, the researchers made a gene "cassette" that contained a Vibrio gene and a marker gene between two copies of the repeat. They inserted the cassette into a circular piece of DNA called a plasmid and allowed it to be taken up by another bacterium, Escherichia coli, which then started using the foreign genes, an indication that they had inserted into E. coli's own integron. Such insertions require an enzyme called an integrase to splice in the genes, and Vibrio had not been known to have this enzyme. So complete proof that the pathogen has an integron came when the Davies team went on to clone the gene for Vibrio's integrase and demonstrate that it has the requisite activity.

Researchers will also want to find out whether bacterial integrons of other species can also pick up genes besides those for antibiotic resistance. But whether or not they do, Vibrio's integron could bode ill for new vaccines being developed against cholera, warns Paul Manning of the University of Adelaide in Australia. He worries that a live vaccine that uses Vibrio strains whose virulence genes have been removed may still be capable of getting new virulence genes through its integron.

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