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New pathogenic bacterium pinpointed

April 14, 2006 By Helen Pearson This article courtesy of Nature News.

Another disease-causing bug has been found.

Scientists have discovered a previously unknown bacterium lurking in human lymph nodes, a finding that suggests there are many more disease-causing bacteria still to be discovered.

The bacterium is thought to cause chronic infections in patients with a rare immune disorder called chronic granulomatous disease (CGD), and the research team is now investigating whether it might be involved in conditions that are more common, such as irritable bowel syndrome.

Researchers know only a fraction of the bacteria that inhabit the water, air and our bodies, because most of them are impossible to grow and identify in the lab. Even when bacteria are suspected as the cause of a disease, it can be extremely difficult to pin down the exact culprit. The digestive disorder Crohn's disease, for example, may be partly caused by bacteria. But researchers have been unable to isolate the bugs that are to blame.

So pinning down a novel disease-causing agent is quite an event. "It's not every day that we find a new organism," says David Greenberg, a lead researcher in the investigation at the National Institute of Allergy and Infectious Diseases (NIAID) in Bethesda, Maryland. The identification of other disease-causing bacteria, such as that responsible for Whipple's disease, found in 1992, or the bug that causes Legionnaires' disease, identified in the 1970s, have caused excitement in the past.

The bacterium is apparently so different from other known germs that the researchers have placed it in its own genus and species - Granulobacter bethesdensis - after the disease and the Bethesda location in which it was found.

Genetic key

Granulobacter bethesdensis was isolated from a CGD patient suffering from fever and weight loss. Having been unable to treat him successfully, the patient's doctors sent him to the specialists at the NIAID. The team removed part of his swollen lymph nodes and embarked on a quest to find the cause of the infection.

They managed to grow the bacteria, but standard identification screens drew a blank. So Greenberg and his colleagues examined a particular gene from the bug whose sequence is often used to work out which bacteria are related to which others.

They found that the mystery bug was most closely related to a family called Acetobacteraceae, whose members were thought to be mostly harmless and are found in fruit, plants and soil. They can contaminate wine and beer fermentation, and are used industrially to make vinegar.

Not so harmless

To prove that the bacterium they had found was causing the problem, the team injected it into mice that had a version of CGD and found that the bacteria also infected the animals' lymph nodes. The researchers have published their results in PLoS Pathogens1 - and have since determined the bacterium's entire genetic sequence.

The pressing question is whether G. bethesdensis infects other people with weak immune systems and whether it is a wider threat to human health, and Greenberg and his colleagues are starting to explore this. Worryingly, it seems to be resistant to most antibiotics. The patient who triggered the investigation still carries an infection.

The investigators have found the bacterium in another two CGD patients with similar symptoms. They have also seen signs of infection in around 5% of healthy people, based on the presence of tell-tale antibodies in the blood. It is possible that the bug regularly invades healthy people, but that most fight it off with no ill effects.

Greenberg is also curious to know where the bug came from originally. "I'd love to scoop up water and dirt and find it," he says. "It has become an all-encompassing project."

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  1. Greenberg D. E., et al. PLoS Pathogens, 2. e28 (2006).


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