Germs Using Iron-clad Protection, Researchers Say

Researchers have documented one of the mechanisms that disease-causing bacteria use to thwart immune-system attacks against them, and it's made of iron.

E. coli and other pathogens use a protein that contains an iron molecule to trigger a genetic reaction to remove nitric oxide that's trying to destroy the germs, the researchers wrote Thursday in the journal Nature.

Nitric oxide is one of the main weapons that immune-system cells use against invaders. The chemical breaks through cell walls to destroy bacteria. But over the past few years, scientists have realized that many bacteria, like E. coli, contain proteins on their surfaces that allow them to neutralize the toxic effects of nitric oxide.

A number of scientists have been working to understand just how the bacteria defend themselves and have focused on several candidates. The new paper spells out one, although probably not the only, mechanism for the disarmament.

"If we can interfere with the mechanism, it could lead to better antibiotics and better treatments," said Stephen Spiro, a Georgia Tech biologist who co-authored the paper with several scientists from Britain's John Innes Centre.

Escherichia coli and its near relative, salmonella, are typically transmitted to humans through undercooked meat, unwashed vegetables and dirty utensils. Infections can cause diarrhea, stomach cramps and sometimes more serious illness that can result in kidney damage and even death.

The federal Centers for Disease Control and Prevention estimates that the most dangerous strain of E. coli infects some 73,000 Americans each year, sending about 2,100 to the hospital and resulting in at least 60 deaths.

E. coli usually doesn't respond to antibiotics, while salmonella has developed several drug-resistant strains.

Spiro and his colleagues studied a harmless strain of E. coli, and focused on a nitric-oxide-regulating protein called NorR. "It turns out that NorR contains a single molecule of iron, and our study found that the nitric oxide binds to the iron, which in turn activates the protein," he explained.

Once the protein is switched on, it ramps up expression of genes that in turn produce an enzyme that removes nitric oxide in large quantities, allowing the bacteria to survive.

The researchers anticipate that by understanding how the bacteria first responds to an onslaught of nitric oxide, they may eventually be able to disrupt this alert system.

Manipulating nitric-oxide levels in the bloodstream is a dicey proposition, since the gas is used to transmit signals between human cells, but also controls inflammation and blood-vessel dilation.

So while some scientists have enjoyed success in using topical therapies using nitric oxide to control infections on the skin and in the mouth, internal use of the substance as a therapy has yet to be worked out.

On the Net: http://www.nature.com