There is an urgent need to find new antibiotics as bacteria are constantly evolving and steadily becoming resistant to the current arsenal used by doctors around the world. A key question is whether it is possible to create better anti-infective agents using design principles rather than by trial and error. Antimicrobial peptides are short protein fragments that have been suggested as such future alternatives to current antibiotics. They identify bacteria and disrupt their membrane structure, thus ultimately killing the bacteria.
A research team consisting of scientists from the London Centre for Nanotechnology (LCN), National Physical Laboratory, University of Edinburgh, University of Oxford, Freie Universität Berlin and IBM, have now used a combination of nanoscale imaging, computer simulation and de novo protein design to reveal a new mechanism of membrane disruption by antimicrobial peptides.
The results uncover a dynamic process whereby peptides form tiny pores, only a few nanometres across, which subsequently expand until they eventually reach the point of complete membrane disintegration. The direct observation of these processes adds to the prevailing models regarding membrane perforation by antimicrobial peptides, revealing a molecular mechanism of active pore expansion.
This offers a physical basis for bacterial membrane disruption which may be useful for drug developers when designing new medicines to combat infections.
Journal link: Nanoscale imaging reveals laterally expanding antimicrobial pores in lipid bilayers, Proc. Nat. Acad. Sci. USA 2013 ; published ahead of print May 13, 2013, doi:10.1073/pnas.1222824110
Figure: Time-lapse atomic force microscopy showing the formation and growth of pores in biological model membranes by antimicrobial peptides