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bioRxiv · 10.1101/388967

Parallel evolution of frog antimicrobial peptides produces identical conformations but subtly distinct membrane and antibacterial activities

Manzo, G.·Ferguson, P. M.·Hind, C.·Clifford, M.·Gustilo, V. B.·Ali, H.·Bansal, S. S.·Bui, T. T.·Drake, A. F.·Atkinson, R. A.·Sutton, M. J.·Lorenz, C. D.·Phoenix, D. A.·Mason, A. J.
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Abstract

Frogs such as Rana temporaria and Litoria aurea secrete numerous closely related antimicrobial peptides (AMPs) as an effective chemical dermal defence. Despite the high similarity in physical properties and preference for adopting secondary amphipathic, -helix conformations in membrane mimicking milieu, their spectrum of activity and potency often varies considerably. Damage or penetration of the bacterial plasma membrane is considered essential for AMP activity and hence distinguishing apparently similar AMPs according to their behaviour in, and effects on, model membranes will inform understanding of species specific effective antimicrobial mechanisms. Here we use a combination of molecular dynamics simulations, circular dichroism and patch-clamp to investigate the basis for differing anti-bacterial activities in representative AMPs from each species; temporin L and aurein 2.5. Despite adopting near identical, -helix conformations in the steady-state in a variety of membrane models, these two AMPs can be distinguished both in vitro and in silico based on their dynamic interactions with model membranes; the greater conformational flexibility and the higher amplitude channel conductance induced offers a rationale for the greater potency and broader spectrum of activity of temporin L over aurein 2.5. Specific contributions from individual residues are identified that define the mechanisms of action of each AMP. Our findings suggest AMPs in frogs are examples of parallel evolution whose utility is based on apparently similar but subtly distinct mechanisms of action.

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Manzo, G., Ferguson, P. M., Hind, C., Clifford, M., Gustilo, V. B., Ali, H., Bansal, S. S., Bui, T. T., Drake, A. F., Atkinson, R. A., Sutton, M. J., Lorenz, C. D., Phoenix, D. A., Mason, A. J.. 2018-08-09. Parallel evolution of frog antimicrobial peptides produces identical conformations but subtly distinct membrane and antibacterial activities. https://doi.org/10.1101/388967

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