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Sugar molecule lights up bacteria

Infection detection Doctors may one day be able to detect harmful bacteria in our bodies before an infection takes hold.

This could potentially prevent the overuse of antibiotics and the development of drug-resistance, as well as save lives.

In a study published online this week in Nature Materials, scientists from the Georgia Institute of Technology report on a new highly-sensitive bacterial detection method in rats.

Lead author Associate Professor Niren Murthy says that, currently, there is no way to specifically and accurately image small numbers of bacteria in vivo.

"The common way would be by CT imaging, where you are just viewing tissue destruction. The problem there is ... it's very hard to distinguish between bacterial infections and many other types of diseases that cause tissue necrosis [damage]," he says.

Bacterial infections that aren't detected until they are well-established can be extremely difficult, and sometimes impossible, to treat. They are the leading cause of limb amputations.

The most dangerous types of infections are those where the bacterial pathogen is living in a community called a biofilm. Biofilms are thousands of times more resistant to antibiotics than free-living bacteria.

Light, camera, action

Murthy says while there are several contrast agents for imaging bacteria that have been used in animals, they either target inflammation caused by bacteria, or the surface of the bacteria.

The Georgia Tech team opted for an agent that could get inside the pathogen.

"We think the big advantage of the maltodextrin transporter, which is what we are targeting, is that the maltodextrin-based imaging probes (MDPs) are internalised by bacteria at a very rapid rate, so you can deliver very high concentrations," he says.

Maltodextrin is a sugar-like molecule that is actively transported into bacterial, but not mammalian cells, giving the bacteria energy. By attaching a fluorescent probe to maltodextrin, the researchers can specifically detect bacteria who have 'gobbled it up.'

The high concentration of probe inside the bacteria ensures that they are clearly visible even when they are present in low numbers.

The scientists demonstrated that a variety of different bacterial species could be detected, including those living in biofilms. They also showed that the MDPs were not taken up by gut bacteria or inactive or dead bacteria.

"This means that it [MDPs] will also be useful in assessing the efficacy of antibiotics ... and whether the bacterial infection has been completely eradicated," says Murthy.

Enormous potential

For the in vivo tests, Murthy and team injected bacteria into the thigh muscle of rats. They then injected the MDPs into the rat's jugular vein so that they could spread throughout the body.

Sixteen hours later, they used a fluorescence imaging system to take photos of the infection site. The bacteria and extent of infection was clearly distinguishable.

Moreover, the MDPs could detect bacterial concentrations 100-fold lower than other imaging agents.

But there is a limitation. Fluorescence, and therefore detection of infection, is only visible up to one centimetre below the skin's surface.

"What we are doing right now is to make MDPs that image bacteria by positron emission tomography (PET imaging) - that will eventually overcome this problem," explains Mirthy.

Professor Ross Barnard, of the University of Queenland says this is a "really neat system with enormous potential". But he says while it is specific to bacteria, it doesn't tell you which type of bacteria is present.

"This is the limitation at the moment ... but it is just an early step along the path. There's room for more development down the track," he says.

"Where there might be an additional application is in attaching therapeutic drugs. You could potentially use it as a delivery vehicle."

According to Murthy, this is already under investigation.

"We have already put an antibiotic on there and think this will be a very good strategy for a new type of antibiotic development, because if we can target the antibiotics directly to the bacteria we won't have to worry about side effects. That gives us more flexibility in terms of what kind of antibiotics we can develop," says Murthy.

Murthy expects it will be at least five years before his team begins human clinical trials.