In the fight against antibiotic resistance, it’s all hands on deck. The clock is ticking and superbugs are spreading, but drug companies are reluctant to create new antibiotics because they’re not money-makers. Researchers may have found a way around that problem by modifying already-existing antibiotics to make them “blow up” deadly superbugs.
University College London (UCL) researchers have found that antibiotics can kill drug-resistant bacteria with sheer brute force – by “pushing” hard enough into bacterial cells. They’ve documented their findings in Nature.
Lead author Dr Joseph Ndieyira, of UCL Medicine, says:
“Antibiotics work in different ways, but they all need to bind to bacterial cells in order to kill them.
Antibiotics have ‘keys’ that fit ‘locks’ on bacterial cell surfaces, allowing them to latch on. When a bacterium becomes resistant to a drug, it effectively changes the locks so the key won’t fit any more.
Incredibly, we found that certain antibiotics can still ‘force’ the lock, allowing them to bind to and kill resistant bacteria because they are able to push hard enough. In fact, some of them were so strong they tore the door off its hinges, killing the bacteria instantly!”
Researchers used sensitive equipment to measure mechanical forces that 4 different antibiotics exerted on bacterial cells, according to a news release. They tested bacteria that were particularly susceptible to antibiotics and bacteria that had become resistant to drugs. The forces the antibiotics exerted on susceptible bacteria were all similar, but the forces exerted by the drugs on resistant antibiotics varied greatly.
The team tested vancomycin, a powerful antibiotic used as a last resort treatment for MRSA and other infections, and oritavancin, a modified version of vancomycin used against complex skin infections.
Oritavancin is fast-acting antibiotic compared to vancomycin, killing bacteria in 15 minutes and 6-24 hours, respectively. Vancomycin disrupts vital processes in bacteria, causing them to slowly stop functioning and die. Oritavancin is technically a modified version of vancomycin, but the new study suggests that it kills bacteria in an entirely different way.
Ndieyira explains in the news release:
“We found that oritavancin pressed into resistant bacteria with a force 11,000 times stronger than vancomycin. Even though it has the same ‘key’ as vancomycin, oritavancin was still highly effective at killing resistant bacteria.
Until now it wasn’t clear how oritavancin killed bacteria, but our study suggests that the forces it generates can actually tear holes in the bacteria and rip them apart.
Oritavancin molecules are good at sticking together to form clusters, which fundamentally changes how they kill bacteria. When two clusters dig into a bacterial surface they push apart from each other, tearing the surface and killing the bacteria. Remarkably, we found that conditions at the bacterial surface actually encourage clustering which makes antibiotics even more effective.”
Ndieyira and his colleagues assembled a detailed mathematical code to show how antibiotics act on the surface of bacterial cells. Researchers will be able to use this model to screen promising new antibiotics that can overpower and kill superbugs.
“Our findings will help us not only to design new antibiotics but also to modify existing ones to overcome resistance. Oritavancin is just a modified version of vancomycin, and now we know how these modifications work we can do similar things with other antibiotics. This will help us to create a new generation of antibiotics to tackle multi-drug resistant bacterial infections, now recognized as one of the greatest global threats in modern healthcare.”