Tracing infections in the body
‘Bacterial infections are a persistent problem for patients. Bacteria like to nestle on implants, for example, infect heart valves or cause pneumonia. It is vital that we trace and treat infections like these as swiftly as possible. That is not easy because an early-stage infection is not visible to the naked eye. We are therefore developing fluorescing molecules that attach themselves to bacteria and illuminate the site of an infection’.
‘It is vital to diagnose infections early. Once an infection takes hold, the bacteria can form a plaque or become encapsulated. This makes them inaccessible to antibiotics, and the infection becomes difficult to treat. People sometimes even need additional surgery to combat the infection. Moreover, prolonged and difficult courses of antibiotics increase the risk of antibiotic resistance.
The biggest challenge is diagnosing and localizing an early infection in a patient. In our lab, we are exploring whether we can do this by using fluorescing molecules that travel to the locus of infection, causing it to shine when illuminated.
The first step in this research is to design and build a fluorescing substance that is specific to bacterial infections. We tried taking an antibiotic molecule – vancomycin – and attaching a commonly-used fluorescent molecule. We know that vancomycin attaches specifically to the cell wall of a particular group of bacteria and not to human cells. Another advantage is the fact that vancomycin is a current and safe drug, which means that the combination molecule is probably safe too.
We now need to carry out tests on tissues and animals to check whether this combination molecule actually works in the way we hope and can be used in patients. We first tested the substance on dead human tissue. After pre-treating the bacterium Staphylococcus epidermidis with the labelled antibiotic, we introduced the labelled bacterium under the skin. Thanks to the fluorescence, this artificial infection was indeed visible through the skin. Although this demonstrated the technical success of the substance, it was still an artificial situation. A tissue model like this obviously lacks any circulation, for example.
Before moving to clinical use on patients, we conducted two animal experiments to test the effect of the substance in vivo. We conducted these experiments in collaboration with colleagues from Germany and the United States. Mice with an infected hind leg were treated with the labelled antibiotic, after which we recorded the site of fluorescence. This indeed proved to be the locus of infection, demonstrating that the principle works. The bladder also lit up, but this was not altogether unexpected because vancomycin is secreted in the urine’.