In order to kill bacteria, antibiotics have to bind to the cells in the pathogens. Bacterial resistance can be caused by molecular changes to the surface of the bacteria.
Dr. Joseph Ndieyira of UCL Medicine said, “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!”
Since antibiotics exert mechanical force on bacteria, researchers used equipment to measure those forces. They tested bacteria that were still susceptible to antibiotics and bacteria that had developed resistance against the drugs. Researchers tested vancomycin, which is a “last resort” treatment for MRSA and other infections, and oritavancin, which s a modified version of vancomycin.
All of the susceptible bacteria received the same amount of ‘force’ from the antibiotics, but the force exerted on resistant bacteria varied. Dr. Ndieyira continued, “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.”
The oritavancin molecules stick together and form clusters, that dig into the surface of bacteria cells. As they do this, they push apart, creating force that tears the bacteria’s surface.
A mathematical model developed by the research team predicts and describes how antibiotics behave in this way, which could be used to screen new antibiotics. And this research could be used to create a new generation of antibiotics.