Amino Acids

, Volume 48, Issue 3, pp 887–900 | Cite as

Rational modification of a dendrimeric peptide with antimicrobial activity: consequences on membrane-binding and biological properties

  • Giovanna Batoni
  • Mariano Casu
  • Andrea Giuliani
  • Vincenzo Luca
  • Giuseppantonio Maisetta
  • Maria Luisa Mangoni
  • Giorgia Manzo
  • Manuela Pintus
  • Giovanna Pirri
  • Andrea C. Rinaldi
  • Mariano A. Scorciapino
  • Ilaria Serra
  • Anne S. Ulrich
  • Parvesh Wadhwani
Original Article

Abstract

Peptide-based antibiotics might help containing the rising tide of antimicrobial resistance. We developed SB056, a semi-synthetic peptide with a dimeric dendrimer scaffold, active against both Gram-negative and Gram-positive bacteria. Being the mechanism of SB056 attributed to disruption of bacterial membranes, we enhanced the amphiphilic profile of the original, empirically derived sequence [WKKIRVRLSA-NH2] by interchanging the first two residues [KWKIRVRLSA-NH2], and explored the effects of this modification on the interaction of peptide, both in linear and dimeric forms, with model membranes and on antimicrobial activity. Results obtained against Escherichia coli and Staphylococcus aureus planktonic strains, with or without salts at physiological concentrations, confirmed the added value of dendrimeric structure over the linear one, especially at physiological ionic strength, and the impact of the higher amphipathicity obtained through sequence modification on enhancing peptide performances. SB056 peptides also displayed intriguing antibiofilm properties. Staphylococcus epidermidis was the most susceptible strain in sessile form, notably to optimized linear analog lin-SB056-1 and the wild-type dendrimer den-SB056. Membrane affinity of all peptides increased with the percentage of negatively charged lipids and was less influenced by the presence of salt in the case of dendrimeric peptides. The analog lin-SB056-1 displayed the highest overall affinity, even for zwitterionic PC bilayers. Thus, in addition to electrostatics, distribution of charged/polar and hydrophobic residues along the sequence might have a significant role in driving peptide–lipid interaction. Supporting this view, dendrimeric analog den-SB056-1 retained greater membrane affinity in the presence of salt than den-SB056, despite the fact that they bear exactly the same net positive charge.

Keywords

Antimicrobial peptides Dendrimers Biofilms Gram-negative Gram-positive Model membranes 

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Copyright information

© Springer-Verlag Wien 2015

Authors and Affiliations

  • Giovanna Batoni
    • 1
  • Mariano Casu
    • 2
  • Andrea Giuliani
    • 3
  • Vincenzo Luca
    • 4
  • Giuseppantonio Maisetta
    • 1
  • Maria Luisa Mangoni
    • 4
  • Giorgia Manzo
    • 5
  • Manuela Pintus
    • 5
  • Giovanna Pirri
    • 3
  • Andrea C. Rinaldi
    • 5
  • Mariano A. Scorciapino
    • 5
  • Ilaria Serra
    • 5
  • Anne S. Ulrich
    • 6
    • 7
  • Parvesh Wadhwani
    • 6
  1. 1.Department of Translational Research and New Technologies in Medicine and SurgeryUniversity of PisaPisaItaly
  2. 2.Department of Chemical and Geological SciencesUniversity of Cagliari, Cittadella UniversitariaMonserrato (CA)Italy
  3. 3.Research and Development UnitSpider Biotech S.r.l.Colleretto Giacosa (TO)Italy
  4. 4.Dipartimento di Scienze Biochimiche, “A. Rossi Fanelli”Istituto Pasteur-Fondazione Cenci Bolognetti, Sapienza Università di RomaRomeItaly
  5. 5.Department of Biomedical SciencesUniversity of Cagliari, Cittadella UniversitariaMonserrato (CA)Italy
  6. 6.Institute of Biological Interfaces (IBG-2)Karlsruhe Institute of Technology (KIT)KarlsruheGermany
  7. 7.Institute of Organic ChemistryKarlsruhe Institute of Technology (KIT)KarlsruheGermany

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