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Last Updated: Thursday, 23 September, 2004, 18:09 GMT 19:09 UK
Science cracks killer bug's code
By Paul Rincon
BBC News Online science staff

Legionella pneumophila, Science Photo Library
Legionella pneumophila: an accidental menace
Scientists have deciphered the complete sequence of DNA in the bacterium that causes Legionnaires' disease.

Infection with the Legionella pneumophila bacterium can be deadly, especially in the elderly or those with compromised immune systems.

As such, it is regarded as a major environmental hazard.

The breakthrough, reported by an international research team in Science magazine, could speed up the search for new vaccines and treatments.

One bacterium can go into a host cell and then replicate into several hundred. The whole host cell becomes a seething mass and explodes
Professor Bill Keevil, University of Southampton
The work, which took four years, was led by Minchen Chien at Columbia University in New York, US, and colleagues from other institutes in America, France and Israel.

It has already highlighted genes that may account for Legionella's extraordinary resistance to man-made disinfectants and its ability to survive in a variety of hosts.

The researchers also identified previously unknown regions of the genome that could be involved in the bug's virulence.

Accidental menace

For it to do any harm to humans, fine droplets containing Legionella bacteria have to be inhaled.

These contaminated aerosols can be released from showers, bath taps, spa pools, decorative fountains, from the cooling towers and evaporative condensers in air conditioning units, and even from the misters in supermarket vegetable cabinets.

Once inside the airways, the bacteria infect macrophages in lung tissue. These are cells that engulf and destroy foreign material. Legionella is thought to mistake these cells for its traditional host, the amoeba. It causes fatal pneumonia in 5-30% of cases.

Legionella is thus not an "obligate pathogen" that needs to cause disease in order to infect other cells, but something of an accidental menace to humans.

"We've got videos showing infected cells. They look like balloons full of worms. One bacterium can go into a host cell and then replicate into several hundred. The whole host cell becomes a seething mass and explodes," Professor Bill Keevil, a Legionella expert at the University of Southampton, UK, told BBC News Online.

A living amoeba (Dictyostellium discoideum) infected with the bacterial pathogen Legionella pneumophila     Margaret Clarke/Science
'Balloon full of worms': an unlucky amoeba infected with Legionella
Co-author Dr James Russo at Columbia said any vaccine for Legionnaires' was unlikely to see widespread use. But it could be administered to those sections of the population that are at special risk.

"We can now start hunting for surface molecules on the bacterium that you might be able to develop an antibody to," Dr Russo said.

"There's an outer membrane protein in Legionella that's well known, but it's highly variable. You would have to look for surface molecules that are not very variable in order for them to be useful in a vaccine. So these might be the things to target now."

The genome work will also raise the possibility of more targeted therapies. Legionnaires' can be treated successfully with the antibiotic erythromycin. But the prognosis can be poor if the disease is caught at a late stage.

"There's a lot of interest in finding something else that buys you another day or so, which could be the difference between life and death for a patient," Professor Keevil explained.

Subversive strategy

Legionella switches off the internal "waste disposal system" macrophages use to destroy any nasty bugs they come into contact with. The way Legionella subverts this defence mechanism could be one of the targets for new treatments.

"You could figure out ways of preventing some of the interactions occurring between the host cell molecules and the molecules in the bacterium. But I don't have a line on how you would do that yet," said Dr Russo.

Legionella in stab culture, CDC
Legionella prefers low oxygen concentrations for growth
Professor Keevil is currently conducting research into the bacteria's prevalence in water systems throughout Europe. He says preliminary data shows they are much more common than previously thought.

Poorly-maintained plumbing systems and air conditioning units are breeding grounds for Legionella. It grows in slimy bacterial colonies attached to surfaces such as the inside of pipes and water tanks. But bacteria can escape from these colonies into water flowing through them.

Scientists at the UK's Health Protection Agency welcomed the genome sequencing, saying it could lead to new diagnostic tools and environmental controls as well as other benefits.

"The true value of such genome sequences lies in their comparative analysis with other microbial genomes," said a spokesperson for the HPA.

"For those working in the field of Legionella this will increase dramatically as the genomes of further strains of L. pneumophila and additional Legionella species are characterised."

The work may also help scientists understand a related bacterial pathogen called Coxiella burnetii, which causes Q Fever. Coxiella is highly infectious and is regarded by the US government as a potential bioterror threat.




SEE ALSO:
Spa pools linked to Legionnaires
13 Sep 04  |  Health
Legionnaires' disease
08 Feb 03  |  Medical notes


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