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

Giorgia Manzo, Philip M. Ferguson, Charlotte Hind, Melanie Clifford, V. Benjamin Gustilo, Hind Ali, Sukhvinder S. Bansal, Tam T. Bui, Alex F. Drake, R. Andrew Atkinson, Mark J. Sutton, Christian D. Lorenz, David A. Phoenix, View ORCID ProfileA. James Mason
doi: https://doi.org/10.1101/388967
Giorgia Manzo
1Institute of Pharmaceutical Science, School of Cancer & Pharmaceutical Science, King’s College London, Franklin-Wilkins Building, 150 Stamford Street, London, SE1 9NH, United Kingdom
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Philip M. Ferguson
1Institute of Pharmaceutical Science, School of Cancer & Pharmaceutical Science, King’s College London, Franklin-Wilkins Building, 150 Stamford Street, London, SE1 9NH, United Kingdom
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Charlotte Hind
2Technology Development Group, National Infection Service, Public Health England, Salisbury, UK
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Melanie Clifford
2Technology Development Group, National Infection Service, Public Health England, Salisbury, UK
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V. Benjamin Gustilo
1Institute of Pharmaceutical Science, School of Cancer & Pharmaceutical Science, King’s College London, Franklin-Wilkins Building, 150 Stamford Street, London, SE1 9NH, United Kingdom
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Hind Ali
1Institute of Pharmaceutical Science, School of Cancer & Pharmaceutical Science, King’s College London, Franklin-Wilkins Building, 150 Stamford Street, London, SE1 9NH, United Kingdom
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Sukhvinder S. Bansal
1Institute of Pharmaceutical Science, School of Cancer & Pharmaceutical Science, King’s College London, Franklin-Wilkins Building, 150 Stamford Street, London, SE1 9NH, United Kingdom
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Tam T. Bui
3Centre for Biomolecular Spectroscopy and Randall Division of Cell and Molecular Biophysics, King’s College London, New Hunt’s House, London SE1 1UL, United Kingdom
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Alex F. Drake
3Centre for Biomolecular Spectroscopy and Randall Division of Cell and Molecular Biophysics, King’s College London, New Hunt’s House, London SE1 1UL, United Kingdom
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R. Andrew Atkinson
3Centre for Biomolecular Spectroscopy and Randall Division of Cell and Molecular Biophysics, King’s College London, New Hunt’s House, London SE1 1UL, United Kingdom
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Mark J. Sutton
2Technology Development Group, National Infection Service, Public Health England, Salisbury, UK
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Christian D. Lorenz
4Department of Physics, King’s College London, London WC2R 2LS, United Kingdom
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David A. Phoenix
5School of Applied Science, London South Bank University, 103 Borough Road, London SE1 0AA, United Kingdom
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A. James Mason
1Institute of Pharmaceutical Science, School of Cancer & Pharmaceutical Science, King’s College London, Franklin-Wilkins Building, 150 Stamford Street, London, SE1 9NH, United Kingdom
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  • ORCID record for A. James Mason
  • For correspondence: james.mason@kcl.ac.uk
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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, α-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, α-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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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted August 09, 2018.
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Parallel evolution of frog antimicrobial peptides produces identical conformations but subtly distinct membrane and antibacterial activities
Giorgia Manzo, Philip M. Ferguson, Charlotte Hind, Melanie Clifford, V. Benjamin Gustilo, Hind Ali, Sukhvinder S. Bansal, Tam T. Bui, Alex F. Drake, R. Andrew Atkinson, Mark J. Sutton, Christian D. Lorenz, David A. Phoenix, A. James Mason
bioRxiv 388967; doi: https://doi.org/10.1101/388967
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Parallel evolution of frog antimicrobial peptides produces identical conformations but subtly distinct membrane and antibacterial activities
Giorgia Manzo, Philip M. Ferguson, Charlotte Hind, Melanie Clifford, V. Benjamin Gustilo, Hind Ali, Sukhvinder S. Bansal, Tam T. Bui, Alex F. Drake, R. Andrew Atkinson, Mark J. Sutton, Christian D. Lorenz, David A. Phoenix, A. James Mason
bioRxiv 388967; doi: https://doi.org/10.1101/388967

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