The gate-crasher from hell

Researchers break bacteria's code only to unlock a startling secret of assimilation. CF sufferers bear the brunt

By Brian Hoyle

As those with cystic fibrosis (CF), burned skin, or a malfunctioning immune system can attest, Pseudomonas aeruginosa infections can be debilitating and, in the case of CF, deadly. Lessened host health can allow P. aeruginosa to use an arsenal of weapons, including multiple antibiotic resistance, to establish a beachhead in the body.

Researchers have now uncovered yet another surprising virulent factor -- an enzyme secreted by P. aeruginosa until now thought to be almost exclusively confined to humans.

A paper presented at the Proceedings of the National Academy of Sciences in the third week of February, chronicled the discovery of the gene for an enzyme called lipoxygenase. In eukaryotes such as ourselves, the enzyme acts to break up fatty acids -- mainly one called arachidonic acid -- which lessens inflammation. The idea that a bacterium would have the enzyme seemed remote, since these types of fatty acids are not present in cells like P. aeruginosa.

Dr John Mekalanos of Harvard Medical School and his colleagues compared the sequences of the genomes of eukaryotes and a variety of bacteria. They were "intrigued " to find that the comparison identified a stretch of the P. aeruginosa genome that was just about identical to the gene for lipooxygenase.

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Further work showed that the bacterial protein was very similar in structure to the eukaryotic version, and was functional. The presence of the enzyme in P. aeruginosa was not a fluke, since examination of a variety of strains kept in the lab culture collection , even from bacteria recovered from CF, showed the enzyme. However, among bacteria the enzyme is pretty rare. Only four other bacterial species out of almost 200 that were examined contained lipoxygenase.

The P. aeruginosa and human enzymes differed in one critical aspect. While the eukaryotic version is locked up inside the host cell, the P. aeruginosa version was secreted from the bacterium to the surrounding environment.

Dr Mekalanos and his colleagues think that in environments such as CF lungs, P. aeruginosa acquired the human version of the enzyme, and modified it to a species that could be secreted to blunt the inflammatory immune responses of the host. That would help the bacteria to survive in the lung and establish a "non-resolving chronic lung inflammation, " say the authors.

Further work will be necessary to confirm that the P. aeruginosa lipoxygenase is the key culprit (or at least a participant) in the ineffective inflammatory response in diseases like CF. But, for now, the study raises the possibility that the production of anti-inflammatory lipid compounds may be a strategy by which pathogens like P. aeruginosa "regulate the host-pathogen relationship. "