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

doi:10.1111/cbdd.13569

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

School of Biomedical Sciences

Research output: Contribution to journal › Article › peer-review

7 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 language	English
Pages (from-to)	1103-1113
Number of pages	11
Journal	Chemical Biology and Drug Design
Volume	96
Issue number	4
Early online date	18 May 2019
DOIs	https://doi.org/10.1111/cbdd.13569
Publication status	Published (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

Funding

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). 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).

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

antimicrobial peptide
biological screening
HDP

Access to Document

10.1111/cbdd.13569Licence: CC BY-NC

Cite this

Gaiser, R. A., Ayerra Mangado, J., Mechkarska, M., Kaman, W. E., van Baarlen, P., Conlon, J. M., & Wells, J. M. (2020). Selection of antimicrobial frog peptides and temporin-1DRa analogues for treatment of bacterial infections based on their cytotoxicity and differential activity against pathogens. Chemical Biology and Drug Design, 96(4), 1103-1113. https://doi.org/10.1111/cbdd.13569

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

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.",

keywords = "antimicrobial peptide, biological screening, HDP",

author = "Gaiser, \{Rogier A.\} and \{Ayerra Mangado\}, Jaione and Milena Mechkarska and Kaman, \{Wendy E.\} and \{van Baarlen\}, Peter and Conlon, \{J. Michael\} and Wells, \{Jerry M.\}",

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: {\textcopyright} 2019 John Wiley \& Sons A/S",

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Gaiser, RA, Ayerra Mangado, J, Mechkarska, M, Kaman, WE, van Baarlen, P, Conlon, JM & Wells, JM 2020, 'Selection of antimicrobial frog peptides and temporin-1DRa analogues for treatment of bacterial infections based on their cytotoxicity and differential activity against pathogens', Chemical Biology and Drug Design, vol. 96, no. 4, pp. 1103-1113. https://doi.org/10.1111/cbdd.13569

Selection of antimicrobial frog peptides and temporin-1DRa analogues for treatment of bacterial infections based on their cytotoxicity and differential activity against pathogens. / Gaiser, Rogier A.; Ayerra Mangado, Jaione; Mechkarska, Milena et al.
In: Chemical Biology and Drug Design, Vol. 96, No. 4, 29.11.2020, p. 1103-1113.

Research output: Contribution to journal › Article › peer-review

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T1 - Selection of antimicrobial frog peptides and temporin-1DRa analogues for treatment of bacterial infections based on their cytotoxicity and differential activity against pathogens

AU - Gaiser, Rogier A.

AU - Ayerra Mangado, Jaione

AU - Mechkarska, Milena

AU - Kaman, Wendy E.

AU - van Baarlen, Peter

AU - Conlon, J. Michael

AU - Wells, Jerry M.

N1 - 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

PY - 2020/11/29

Y1 - 2020/11/29

N2 - 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.

AB - 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.

KW - antimicrobial peptide

KW - biological screening

KW - HDP

UR - https://www.scopus.com/pages/publications/85075429386

U2 - 10.1111/cbdd.13569

DO - 10.1111/cbdd.13569

M3 - Article

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AN - SCOPUS:85075429386

SN - 1747-0277

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EP - 1113

JO - Chemical Biology and Drug Design

JF - Chemical Biology and Drug Design

IS - 4

ER -

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

Abstract

Bibliographical note

Funding

UN SDGs

Keywords

Access to Document

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