Watching an infection take hold in 3D and in real time

What does an infection look like as it takes hold in the body? Where does it spread to and when? When does the immune system kick in and drive the infection off?

For the first time, scientists at the new MRC Centre for Molecular Bacteriology and Infection at Imperial College London have used scanning equipment to watch an infection unfurl, in real time, inside an animal.

"I saw this and just said wow!" was the instant response of Prof Gadi Frankel, when he first viewed the scans.

"This allows us for the first time to visualise infection in 3D in real time."

The video shows bacteria infecting the small intestine, retreating to a small pocket in the digestive tract and the booming in numbers as they spread to the rectum then all over the large intestine.

The later scans show the immune system driving the bacteria back and the mouse clearing the infection.

Bacterial light

It works by measuring tiny quantities of light produced by the bacteria, which escape from inside the mouse.

The researchers used a genetically modified version of a mouse bug, Citrobacter rodentium, which produces light.

Dr James Collins, who works in Prof Frankel's lab, then puts the infected mice inside the scanner.

"It is a dark box which keeps the animals warm and blocks any other light from coming in. It has a camera at the top so we can very sensitively measure any light that's emitted through the mouse by the bacteria."

He then uses the measurements to build up a map of the exact location of the bacteria in different parts of the body. The amount of light escaping shows how many bacteria there are. More light means more bacteria and if the light starts to go out then that means the bacteria are being killed off.

Repeating these scans, with the same mouse, day after day, builds a complete picture of an infection.

The equipment can also be configured to look in exquisite detail at the immune system. Dr Collins said: "We can image where the bacteria are and where and which types of immune cells have been recruited to that area."

'Revolution'

Prof Frankel said: "It is something which will revolutionise the way we study bacterial infection, this is the future."

He hopes this technology will help with some of the most pressing issues in medicine.

"The big problem of course is the rise of antibiotic resistance, this is the major challenge we are facing at the moment," he said.

There are also issues about new emerging bugs such as the E. coli O104 outbreak in Germany last year and the constant need for new and better vaccines.

"We would be able to visualise how antibiotics and vaccination works in a living animal - that's something which was never done before.

"It will give us incredibly important tools to develop better vaccines and better antibiotics, which will allow us to tackle bacterial infections in the future," Prof Frankel added.

The scans would show how different vaccines and antibiotics change the way bacteria take over different parts of the body, which could help researchers screen for the most promising options.

They have also done some experiments with probiotic yoghurts. They have shown that using "good bacteria" changes the way an infection takes hold, which may benefit the mouse.

Dr James Collins concluded: "We're only just scratching the surface of what we're able to do with it really."