Exploring Bacteria-Destroying Proteins for More Efficient Antibiotics
News Oct 09, 2013
A research team, led by the National Physical Laboratory (NPL), has carried out studies into how protein fragments found in our bodies destroy harmful bacteria .
The protein fragments, known as antimicrobial peptides, have fought bacteria in the human body for thousands of years by identifying and disrupting the structure of the bacterial membrane. But little is still known about the precise mechanisms they use to carry out this process. The NPL-led team conducted two separate studies to better understand the process and help assess the feasibility of using human antimicrobial peptides as the basis of new treatments.
The first study used de novo protein design and nanoscale imaging techniques, Atomic Force Microscopy and high resolution Mass Spectrometry, together with computer simulations. This combination, never used before for this application, allowed the scientists to study how the peptides destroy the bacteria on a molecular level.
The research, reported in PNAS, revealed that the peptides form nanoscale pores in the bacterial membranes, which subsequently expand until the membrane completely disintegrates. In targeting the membrane, a heterogeneous structure composed predominantly of proteins and lipids, it is thought that the peptides reduce the likelihood that bacteria will develop resistance. This is because many genes would need to mutate simultaneously in order to do so – a very unlikely scenario.
However, before they are considered for medical use, it is important that scientists understand the likelihood of bacteria becoming resistant to the peptides. A second NPL-led study looked to do just that, using a combination of measurements, imaging and molecular dynamics simulations. It explored whether and how bacteria could develop resistance to these antibiotic peptides as they have to conventional antibiotics like methicillin.
The findings, reported in the Journal of Biological Chemistry, suggest that antagonistic peptide chains secreted by bacterial cells or expressed on their surfaces may cause efficient anti-antimicrobial responses, meaning that bacteria could potentially thrive in the presence of the peptides. This discovery may give scientists a better understanding of bacterial resistance and help them choose the right approach when developing the peptides for medical use.
Dr. Max Ryadnov, who leads NPL's scientific research in Biotechnology, said: “It is widely known that these antimicrobial peptides are very efficient at destroying bacteria, but previous measurement techniques only let us see to a detail of five nanometres. The unique combination of technologies used in this research allowed us to see the process at larger length scales and in finer detail. The implications of these research efforts could be considerable - potentially paving the way for an alternative to the current, increasingly inefficient, antibiotic treatments, but also helping us understand the potential vulnerabilities of therapeutics based on these peptides.”
The research was led by NPL and featured scientists from the London Centre for Nanotechnology, UCL, University of Edinburgh, University of Bristol, University of Oxford, Freie Universität Berlin and IBM.
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