Spotting lung infections with glowing bacteria

Around the world, about 20 million people need a ventilator to breathe. Ventilator patients are some of the most critically ill, and they are particularly vulnerable to picking up lung infections like pneumonia. But, because time is so short for these patients, doctors don’t have time to properly diagnose the infection, which can take days, and so they end up being given lots of emergency antibiotics. As well as using up resources, this adds to the already significant global problem of antibiotic resistance.

Now, scientists have developed a new way of rapidly seeing bacteria in patients’ lungs at the hospital bedside, which they hope could be used to confirm a suspected diagnosis within seconds, and also monitor the progress of treatments. Clinician and researcher Kev Dhaliwal from the University of Edinburgh took part in the research, and he spoke to Katie Haylor...

Kev - One of the biggest challenges faced by humanity at the moment is the rise of antimicrobial resistance and the lack of antibiotics we have in the pipeline. We need to better steward what we have currently, but also to make sure we’re giving the right class of antibiotics to the patient otherwise we drive resistance. And in some scenarios, such as intensive care with very sick patients, we give very broad spectrum antibiotics. We need to stop antibiotics that we don’t need to give because there are many side effects and also it drives resistance. So the idea here was to develop a bedside technology that could give us the results within seconds.

Katie - Can you walk us through your new technique?

Kev - You can call them “molecular light bulbs” or “fluorescent Smarties.” They’re chemicals that will bind to targets, and light up when they bind to the target. We spray them into the area we’re interested in, then we pass a small microscope and look for this light and that’s what we’re seeing. So the paper and the work we describe is the ability to spray these ‘smart probes’ as we call them, or these molecular light bulbs in. They hit the target and they light up, and we actually take the detector right into the distal part of the lung.

Katie - So you’ve got a molecule which is capable of emitting a light signal and that’s what, bound to something that reacts to the bacteria?

Kev - Yeah. The core technology was around an antibiotic that we modified that only binds to certain types of bacteria that we then put this fluorophore on, and it only lit up when it touched that bacteria. So the fluorophore embeds itself into the membrane of a bacteria, and the membrane of bacteria have got different environments that can make fluorophore light up from zero to high levels.

Katie - So what information do you end up with then at the bedside?

Kev - We start seeing clumps of bacteria sparkling in front of us. One of the biggest challenges we have to do now is to understand whether that is just bacteria that were there already and what levels there were, or is this a real infection. So what we’re trying to do in studies moving forwards is now take this out to many more patients now that we’ve proven we can see the bacteria in the lung. And in the small series that we’ve done, we think that indicates real new infection to validate that in hundreds of people to show that we can actually definitively diagnose this condition - pneumonia - within sixty seconds on a ventilator.

We also have other molecular light bulbs that pick up other signatures of infection, so inflammatory cells for instance. So we’d like to think of this as a bit like a rainbow: green is the light we’re seeing in the bacteria but can also pick up red, magenta and other signals when we put other smart probes in. So what we’re about to do now is take this to the next level. We’re going to actually spray in a combination of these probes that pick up both inflammation, which is the host’s or the human’s response to infection, and the bacteria to give us this unique signature. These are not just bacteria that are sitting there, these are bacteria that are actually causing nasty damage.

We have developed now probes that tell us the class of bacteria. That can direct the type of antibiotic we give. So what we’re moving towards is actually the ability for these smart probes to also be able to tell us that the bacteria are alive or dead. Now that wasn’t part of this study that we published, but that’s where we’re moving to, the ability to show that antibiotics are actually working. Because often we give antibiotics and we don’t know the dose that we’re giving is correct in these patients, and we’re not entirely sure whether they penetrate the tissue to kill the bacteria, so monitoring treatment efficacy is a key goal.

Katie - Can you give us an indication of how significant this new technique could be?

Kev - We spent many years and decades as scientists using animal models or things in dishes and thinking we know what’s going on inside a human being. We’ve never been able to actually see real bacteria real infections in humans before at the bedside in patients who are acutely unwell. But the ability now, to do molecular microscopy inside human beings, we can actually understand disease processes so I think, from our perspective, we’re excited because it’s the beginning of that journey.