University of Hertfordshire

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Original languageEnglish
Article number9134
Pages (from-to)1-19
Number of pages19
JournalInternational Journal of Molecular Sciences
Early online date30 Nov 2020
Publication statusPublished - 30 Nov 2020


Cationic antimicrobial peptides have attracted interest, both as antimicrobial agents and for their ability to increase cell permeability to potentiate other antibiotics. However, toxicity to mammalian cells and complexity have hindered development for clinical use. We present the design and synthesis of very short cationic peptides (3-9 residues) with potential dual bacterial membrane permeation and efflux pump inhibition functionality. Peptides were designed based upon in silico similarity to known active peptides and efflux pump inhibitors. A number of these peptides potentiate the activity of the antibiotic novobiocin against susceptible Escherichia coli and restore antibiotic activity against a multi-drug resistant E. coli strain, despite having minimal or no intrinsic antimicrobial activity. Molecular modelling studies, via docking studies and short molecular dynamics simulations, indicate two potential mechanisms of potentiating activity; increasing antibiotic cell permeation via complexation with novobiocin to enable self-promoted uptake, and binding the E. coli RND efflux pump. These peptides demonstrate potential for restoring the activity of hydrophobic drugs.


Funding Information: Funding: Tadeh Tahmasi was partially supported by a Wellcome Vacation Scholarship (202526/Z/16/Z). Pedro de Resende and Sarah Soares were supported by CAPES‐Brazil (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior). Funding Information: Acknowledgments: Ilaria Passarini was supported by a University of Hertfordshire PhD studentship. Publisher Copyright: © 2020 by the authors. Licensee MDPI, Basel, Switzerland.

Research outputs

ID: 19036860