Science vs Superbugs

 

When we find ourselves in a medical crisis, often our first move is to head for the hospital. In the UK, more than 15 million people pass through hospital doors every year. But for an unlucky few, this may mean leaving with more problems than they came in with.

 

Of every 100 patients that find themselves in hospital worldwide, between seven and ten will contract at least one new infection during their stay. Known as ‘nosocomial’ or ‘hospital-acquired’ infections (HAIs), the resulting conditions can be very difficult to treat. The majority of HAIs can usually be controlled using a combination of different antibiotics and drugs. But we’re now seeing growing signs of resistance amongst some bacteria, dubbed ‘superbugs’, which creates a very real threat to the safety of our clinical spaces and may make certain routine procedures dangerous.

 

Respiratory, urinary tract and surgical site infections are some of the most common HAIs in the UK, and many of the bacteria associated with these illnesses are becoming increasingly resistant to all but the last-line of defence: an antibiotic called vancomycin. It works by attacking the bacteria’s cell wall. Targeting the proteins that build this defensive barrier around the bacterial cell, the antibiotic can prevent the barrier from forming, leaving the bacteria open to attack. In recent years we’ve seen some bacteria evolving the ability to sidestep this action and form a protective wall anyway. This makes them resistant to vancomycin.

 

As vancomycin is generally a very effective antibiotic, we save it for all but the most serious of cases. We don’t want bacteria to get too used to it, because the more contact that a disease producing agent has with a drug, the quicker it’s able to evolve resistance.

What’s more, resistance can ‘jump’ between bacterial species by swapping useful genes. If one type of infection becomes resistant, others in the same environment can also develop resistance as a result – and in a clinical setting, this effect becomes even more pronounced.

 

Scientists are particularly concerned about Methicillin-resistant Staphylococcus Aureus (MRSA), a common hospital infection, ‘learning’ vancomycin-resistance from other bacteria. Were this to happen, it would eliminate one of the last drugs currently effective at treating this superbug.

It’s clear that if we allow this situation to continue, we could soon see many HAIs becoming increasingly difficult to treat. But scientists are working to find solutions to antibiotic-resistance in hospital infections.

Research on Diamond’s Circular Dichroism (read more about this technique in Inside Diamond Issue 8, see below magazine as PDF or FlippingBook) beamline, is particularly focused on combatting a type of bacteria called Enterococci, which causes a range of HAIs including meningitis, urinary tract infections and bacterial endocarditis. Enterococci is a genus of bacteria with both high antibiotic resistance and high prevalence in hospitals. It also happens to be resistant to vancomycin – bad news in the fight against superbugs.

 

How exactly has it managed this? VanS, the membrane protein in enterococci bacteria, controls resistance to vancomycin. Located within the bacteria’s cell wall, it’s a sensory protein which helps the bacteria respond to threats.

When VanS comes into contact with a certain trigger molecule, it provokes a reaction in the bacteria’s proteins that activates the mechanisms for resistance. So we know this is the protein that protects some of the worst HAIs from the vancomycin antibiotic, but we’re just not sure what the trigger is that sets the whole process off.

 

If we can solve that missing piece of the puzzle, it may be possible to design inhibitors that get in the way of any interaction between VanS and the trigger molecule, thus preventing the bacteria from activating its defence mechanisms. And now, scientists from the University of Central Lancashire and Diamond think they may have discovered that vital missing link: the trigger molecule.

They recently provided evidence to show that proteins within vancomycin unintentionally bind to VanS, activating the bacteria’s resistance mechanism. And so in a strange twist, it appears that the antibiotic itself is the agent that helps the bacteria to better protect itself.

But this isn’t the end of the matter. There may be more than one trigger that activates enterococci’s resistance mechanism. If we’re to effectively shut the process down, we need to get in the way of all potential triggers, not just one.

 

Nonetheless, now that we know about the triggering relationship between vancomycin, the proteins and bacterial resistance, we’re one big step closer towards designing inhibitors that shut off the activation process that leads to resistance in some of the worst hospital acquired infections.

Medical professionals and hospital staff work incredibly hard to keep us safe when we spend time on the ward; in this endeavour they are joined by pioneering scientists who are taking the fight directly to antibiotic resistant bacteria, to help ensure we all check out with a clean bill of health.