London: Nano-probes show how antibiotics work

Research lead

Scientists at the London Centre for Nanotechnology, based at UCL, have developed novel, ultra-sensitive nanomechanical probes capable of providing new insights into how antibiotics work, and paving the way for the development of more effective new drugs.

The researchers led by Rachel McKendry and Gabriel Aeppli with support from the specialist product development consultancy, Bio Nano Consulting (BNC), studied the mode of action of vancomycin, one of the few antibiotics that remains effective against resistant infections such as MRSA

The researchers used cantilever arrays – tiny levers no wider than a human hair – to examine the process which takes place in the body when vancomycin binds to the surface of the bacteria. They coated the cantilever array with mucopeptides from bacterial cell walls and found that as the antibiotic attaches itself, it generates a surface stress on the bacteria which can be detected by a tiny bending of the levers. The researchers suggest that this stress contributes to the disruption of the cell walls and the breakdown of the bacteria.

The team then went on to compare how vancomycin interacts with both non-resistant and resistant strains of bacteria. So-called superbugs become resistant to antibiotics because of a single mutation which deletes a hydrogen bond from their cell walls. This small change makes it approximately 1,000 times harder for the antibiotic to attach itself to the cell wall, and renders them therapeutically ineffective.

McKendry said, “The cell wall is weakened by the antibiotic, ultimately killing the bacteria. Our research on cantilever sensors suggests that the cell wall is disrupted by a combination of local antibiotic-mucopeptide binding and the spatial mechanical connectivity of these events. Investigating both these binding and mechanical influences on the cells’ structure could lead to the development of more powerful and effective antibiotics in future.”

David Sarphie, Bio Nano Consulting CEO said, “BNC was set up specifically to help companies apply nanotechnology tools to address real-world biomedical problems such as antimicrobial resistance. Working with the BNC allows companies access [to] scientists who have expertise in numerous ground-breaking nanotech-related research areas.

BNC was set up in 2007 to provide a seamless concept-to-market route for the bio-nanotechnology sector.