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Three Genomes and Whooping Cough

By Edward R. Winstead

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The bacterium that causes whooping cough, B. pertussis, releases toxins that inflame the throat and lungs.

With the goal of developing new vaccines against whooping cough, scientists have sequenced the genome of the bacterium that causes the disease and discovered a whole family of proteins that might be used in vaccines.

New vaccines are needed because the incidence of the disease seems to be rising in parts of the world, and some strains of the bacterium may be resistant to the current regimen.

“The big picture aim of the sequencing was to find better vaccines,” says Duncan J. Maskell of the University of Cambridge, the United Kingdom, who co-led the project. “But we knew many interesting things would result from sequencing the bacterium.”

In addition to the proteins, another interesting discovery was a set of genes the bacterium may use to make a capsule around itself. The discovery was a surprise because few scientists thought the bacterium, called Bordetella pertussis, made a capsule.

Even now, it’s not clear that the bacterium does make a capsule, but the researchers are trying to resolve the question because the capsule, if one exists, could be a target for drugs or vaccines.

B. bronchiseptica causes respiratory disease in many animals, including dogs, cats, and pigs.
“We’re still looking,” says Maskell. “Some capsules can be extremely difficult to see, but the fact that the genes are there has encouraged us to look a bit harder.”

Whooping cough is highly contagious. It causes more then 200,000 deaths worldwide, mostly among unvaccinated children in developing countries. The disease is named for the “whoop” sound a person makes during coughing attacks.

The project included the sequencing of two close relatives of B. pertussis as a way to learn about its biology. One relative, Bordetella parapertussis, infects both humans and sheep, and tends to cause milder forms of whooping cough.

The other relative, Bordetella bronchiseptica, infects the lungs of many animals, including dogs, cats, and pigs; humans are rarely infected. The bacterium can cause no disease symptoms or chronic respiratory problems. Infectious outbreaks occur in places like boarding kennels and veterinary clinics.

DNA differences among the genomes seem to correspond to differences in traits. Specifically, the traits are 1) the types of diseases each bacterium causes and 2) the organisms they infect. The findings were published in Nature Genetics.

Based on the content of their genomes, the researchers conclude that two of the species were derived from an ancestor of B. bronchiseptica. The other two species have lost significant blocks of genes during the course of evolution, which may explain why they infect fewer organisms than B. bronchiseptica.

The researchers say that B. bronchiseptica probably has not acquired genes that allow it to infect a greater range of hosts than the other species. Indeed, they find no evidence that any of the three has acquired large blocks of genes over recent evolutionary time.

Rather, it is the inactivation of genes present in the ancestral species that accounts for differences between B. bronchiseptica and the two derivative species.

A fourth Bordetella species—one that infects turkeys—is being sequenced now and should be finished in the coming months. It will add another dimension to the evolutionary history of whooping-cough bacteria.

—Related Articles—

To Make a Vaccine, First Sequence a Genome

For more information about whooping cough vaccines visit the World Health Organization.

Parkhill, J. et al. Comparative analysis of the genome sequences of Bordetella pertussis, Bordetella parapertussis and Bordetella bronchiseptica. Nat Genet 35, 32-40 (September 2003).

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