8 July 2003 17:00 GMT

by Julie Clayton

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Melbourne, Australia - The bacterium that causes whooping cough in humans, Bordetella pertussis, has achieved its present dubious status by 'losing' the normal constraints on virulence. It's the cost of modern-day living, with humans in dense populations, that allows this to happen, says a microbial genomics expert.

Analysis of the genome sequence of B. pertussis shows that major changes in its genetic make-up have occurred over a relatively short length of time, enabling it to lose the activity of genes that would normally control virulence.

In this respect, it bears similarities to other bacterial pathogens, such as Salmonella typhi, which causes typhoid fever, and Yersinia pestis, the agent of the plague, says Julian Parkhill of The Sanger Centre near Cambridge, UK.

In ancestral forms of these species, these controls would have ensured that the bacteria did not kill their hosts before they could be transmitted to others. But increasingly frequent contact between people has altered the balance of tradeoff between virulence and pathogenicity, or tendency to spread, and the bacteria can afford to drop the controls.

Parkhill and his colleagues have compared the B. pertussis genome with that of B. parapertussis, which has a broader host range, and B. bronchiseptica, both of which are capable of surviving in the environment outside their hosts.

Most changes that have occurred in the evolution of B. pertussis involve gene deletion and gene loss by mutation, says Parkhill, particularly involving genes that code for cell-surface, regulatory, and transport proteins. But even minor changes can have dramatic effects: just a few base-pair changes are responsible for the increased expression of the pertussis toxin ptxA in B. pertussis, they revealed here at the International Congress of Genetics 2003.

These results echo previous findings from the comparison of S. typhi with S. typhimurium, which has a broader host range, is non-pathogenic to humans, but causes disease in mice. Around 18% of the S. typhi genome is made up of about 200 "pseudogenes" - genes that previously had a role in ancestral Salmonella, but which have become inactivated through mutation.

The result is an organism with a narrower host range but one that has greater virulence owing to its ability to move via the blood stream and cause systemic infection, rather than remaining restricted to the gut.

"The enteric bacteria as a whole are continuously exchanging genetic material and there's continuous acquisition of material and gene loss," said Parkhill. As soon as they find themselves in a position to do so, they'll take advantage of a new environment, he says, and start adjusting into their new niche. "They're very opportunistic," he added. "The world is full of bacteria, and they're all available to take advantage of any opportunity that we give them.

For other stories from ICG 2003, click through to BioMedNet Conference Reporter.