Abstract
We have collected several observations of threshold events in the interactions of antimicrobial peptides (AMPs) with model membranes. These, however, usually occur very close to full membrane coverage. Because such events are frequently disruptive (lysis, pore formation, charge neutralization) we hypothesize a link between these and the antibacterial activity of the peptides. We then establish a mathematical relationship between the biophysical properties of AMPs and threshold events in the bacterial membrane, and demonstrate that high membrane coverage is not only physiologically plausible but also a likely requirement for AMP activity. In agreement, a co-occurrence of bacterial death and surface charge neutralization was observed using zeta-potential measurements of E. coli suspensions treated with the AMP BP100:View Large Image | View Hi-Res Image | Download PowerPoint SlideOur model further allows the prediction of biologically-observed AMP activities (the minimum inhibitory concentrations) from biophysical parameters of peptide-membrane interaction. This approach successfully predicted the activities of two different AMPs against a set of susceptible strains.[1] M.N. Melo, R. Ferre and M.A.R.B. Castanho, Nature. Rev. Microbiol, 2009, 7:245[2] C.S. Alves, M.N. Melo, et al., J. Biol. Chem., 2010, 285:27536.[3] R. Ferre∗, M.N. Melo∗, et al., Biophys. J., 2009, 96:1815.
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