Certain antibiotics exert more force at the surface of drug-resistant bacteria cells.
New findings suggest that antibiotics may be able to kill resistant bacteria if they use enough force to break into the bacterial cells, according to a study published by Nature Scientific Reports.
This method could be a promising way to overcome antibiotic resistance, and may even lead to the development of more effective drugs.
"Antibiotics work in different ways, but they all need to bind to bacterial cells in order to kill them," said lead study author Joseph Ndieyira, PhD. "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!"
The investigators measured the mechanical forces that were exerted on bacterial cells by 4 different types of antibiotics, and tested bacteria that were and were not resistant to the drugs.
The study authors found that antibiotics exerted similar force on susceptible bacteria, but the force varied among resistant bacteria, according to the study. Specifically, the researchers noted the findings from vancomycin, a last resort antibiotic to treat MRSA and other infections, and a modified version of the drug that can be used to treat complex skin infections.
"We found that oritavancin pressed into resistant bacteria with a force 11,000 times stronger than vancomycin," Dr Ndieyira said. "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 is an antibiotic that kills bacteria within 15 minutes, while vancomycin can take up to 24 hours. Vancomycin disrupts a cellular process that causes bacteria to stop functioning and die.
Although oritavancin is a is a modified version of vancomycin, the findings suggest that the 2 drugs may kill bacteria in a completely different manner, according to the study.
"Oritavancin molecules are good at sticking together to form clusters, which fundamentally changes how they kill bacteria," said Dr Ndieyira. "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."
The authors created a mathematical model to determine how antibiotics attack the surface of bacterial cells. The new model could be used to screen new antibiotics to identify how much force they exert when in contact with bacteria, according to the study.
"Our findings will help us not only to design new antibiotics but also to modify existing ones to overcome resistance," Dr Ndieyira said. "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."