Nanotechnology gives insight into workings of antibiotics for
16 October 2008
Scientists from the London Centre for Nanotechnology (LCN) at
University College London (UCL) are using a novel nanomechanical
approach to investigate the workings of vancomycin, one of the few
antibiotics that can be used to combat increasingly resistant infections
such as MRSA.
The researchers, led by Dr Rachel McKendry and Professor Gabriel
Aeppli, developed ultra-sensitive probes capable of providing new
insight into how antibiotics work, paving the way for the development of
more effective new drugs. A report on the research was published in this
week's Nature Nanotechnology journal (12 October).
During the study Dr McKendry, Joseph Ndieyira, Moyu Watari and
coworkers used cantilever arrays — tiny levers no wider than a human
hair — to examine the process which ordinarily takes place in the body
when vancomycin binds itself 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 team suggests that this stress contributes to the disruption
of the cell walls and the breakdown of the bacteria.
The interdisciplinary team went on to compare how vancomycin
interacts with both non-resistant and resistant strains of bacteria. The
'superbugs' are resistant to antibiotics because of a simple mutation
which deletes a single hydrogen bond from the structure of their cell
walls. This small change makes it approximately 1,000 times harder for
the antibiotic to attach itself to the bug, leaving it much less able to
disrupt the cells' structure, and therefore therapeutically ineffective.
"There has been an alarming growth in antibiotic-resistant hospital
'superbugs' such as MRSA and vancomycin-resistant Enterococci (VRE),"
said Dr McKendry. "This is a major global health problem and is driving
the development of new technologies to investigate antibiotics and how
"The cell wall of these bugs is weakened by the antibiotic,
ultimately killing the bacteria," she continued. "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."
"This work at the LCN demonstrates the effectiveness of silicon-based
cantilevers for drug screening applications," added Professor Gabriel
Aeppli, Director of the LCN. "According to the Health Protection Agency,
during 2007 there were around 7,000 cases of MRSA and more than a
thousand cases of VRE in England alone. In recent decades the
introduction of new antibiotics has slowed to a trickle but without
effective new drugs the number of these fatal infections will increase."
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