Selection of antimicrobial frog peptides and temporin-1DRa analogues for treatment of bacterial infections based on their cytotoxicity and differential activity against pathogens

Rogier A. Gaiser, Jaione Ayerra Mangado, Milena Mechkarska, Wendy E. Kaman, Peter van Baarlen, J. Michael Conlon, Jerry M. Wells

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

Abstract

Cationic, amphipathic, α-helical host-defense peptides (HDPs) that are naturally secreted by certain species of frogs (Anura) possess potent broad-spectrum antimicrobial activity and show therapeutic potential as alternatives to treat infections by multidrug-resistant pathogens. Fourteen amphibian skin peptides and twelve analogues of temporin-1DRa were studied for their antimicrobial activities against clinically relevant human or animal skin infection-associated pathogens. For comparison, antimicrobial potencies of frog skin peptides against a range of probiotic lactobacilli were determined. We used the VITEK 2 system to define a profile of antibiotic susceptibility for the bacterial panel. The minimal inhibitory concentration (MIC) values of the naturally occurring temporin-1DRa, CPF-AM1, alyteserin-1c, hymenochirin-2B, and hymenochirin-4B for pathogenic bacteria were threefold to ninefold lower than the values for the tested probiotic strains. Similarly, temporin-1DRa and its [Lys4], [Lys5], and [Aib8] analogues showed fivefold to 6.5-fold greater potency against the pathogens. In the case of PGLa-AM1, XT-7, temporin-1DRa and its [D-Lys8] and [Aib13] analogues, no apoptosis or necrosis was detected in human peripheral blood mononuclear cells at concentrations below or above the MIC. Given the differential activity against commensal bacteria and pathogens, some of these peptides are promising candidates for further development into therapeutics for topical treatment of skin infections.

Original languageEnglish
Pages (from-to)1103-1113
Number of pages11
JournalChemical Biology and Drug Design
Volume96
Issue number4
Early online date18 May 2019
DOIs
Publication statusPublished (in print/issue) - 29 Nov 2020

Bibliographical note

Funding Information:
The authors thank Dr. Arshnee Moodley from the University of Copenhagen and Dr. John Hays from Erasmus University Medical Centre Rotterdam (EMC) for making their bacterial isolates available. This study has been funded by the Marie Curie Actions under the Seventh Framework Programme for Research and Technological Development of the EU (Grant Agreement 289285).

Funding Information:
The authors thank Dr. Arshnee Moodley from the University of Copenhagen and Dr. John Hays from Erasmus University Medical Centre Rotterdam (EMC) for making their bacterial isolates available. This study has been funded by the Marie Curie Actions under the Seventh Framework Programme for Research and Technological Development of the EU (Grant Agreement 289285).

Publisher Copyright:
© 2019 John Wiley & Sons A/S

Keywords

  • antimicrobial peptide
  • biological screening
  • HDP

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