In vivo activity and low toxicity of the second-generation antimicrobial peptide DGL13K

Sven Ulrik Gorr; Craig M. Flory; Robert J. Schumacher

doi:10.1371/journal.pone.0216669

In vivo activity and low toxicity of the second-generation antimicrobial peptide DGL13K

Sven Ulrik Gorr, Craig M. Flory, Robert J. Schumacher

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32 Scopus citations

Abstract

Antimicrobial peptides have been evaluated as possible alternatives to traditional antibiotics. The translational potential of the antimicrobial peptide DGL13K was tested with focus on peptide toxicity and in vivo activity in two animal models. DGL13K was effective against Pseudomonas aeruginosa, Staphylococcus aureus and methicillin-resistant S. aureus with minimal bactericidal concentrations similar to the minimal inhibitory concentration. The peptide showed low toxicity to human red blood cells and HEK cells with median lethal dose around 1 mg/ml. The median lethal dose in greater wax moth larvae (Galleria mellonella) was about 125mg/kg while the peptide caused no skin toxicity in a mouse model. A novel high-throughput luminescence assay was used to test peptide activity in infected G. mellonella, thus reducing vertebrate animal use. DGL13K killed P. aeruginosa in both the G. mellonella model and a mouse burn wound infection model, with bacterial viability 3-10-fold lower than in untreated controls. Future experiments will focus on optimizing peptide delivery, dose and frequency to further improve the antibacterial effect.

Original language	English (US)
Article number	e0216669
Journal	PloS one
Volume	14
Issue number	5
DOIs	https://doi.org/10.1371/journal.pone.0216669
State	Published - May 2019

Bibliographical note

Funding Information:
SUG supported by the National Center for Advancing Translational Sciences of the National Institutes of Health Award Numbers grant UL1TR002494 and UL1 TR002377. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Additional support was provided from the Minnesota Partnership for Biotechnology and Medical Genomics through the Translational Product Development Fund (TPDF) and the University of Minnesota School of Dentistry, NIH.gov, www.dentistry.umn.edu. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We thank Lia Coicou, Brenda Koniar, Niki Larson, Margaret Mysz, and Beverly Norris from CTM for assistance with the mouse infection model and Austin McCullough, University of Minnesota School of Dentistry, for preliminary experiments with the G. mellonella model. Maria Giner Navalon is thanked for performing the HEK cell experiments as a visiting research student from the Universitat Internacional de Catalunya, Faculty of Dentistry, Barcelona, Spain. We thank Jennifer Nilson and Gary Dunny, Department of Microbiology and Immunology, University of Minnesota, for making the S. aureus strain USA300 LAC available for this research.

Publisher Copyright:
© 2019 Gorr et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

PubMed: MeSH publication types

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

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title = "In vivo activity and low toxicity of the second-generation antimicrobial peptide DGL13K",

abstract = "Antimicrobial peptides have been evaluated as possible alternatives to traditional antibiotics. The translational potential of the antimicrobial peptide DGL13K was tested with focus on peptide toxicity and in vivo activity in two animal models. DGL13K was effective against Pseudomonas aeruginosa, Staphylococcus aureus and methicillin-resistant S. aureus with minimal bactericidal concentrations similar to the minimal inhibitory concentration. The peptide showed low toxicity to human red blood cells and HEK cells with median lethal dose around 1 mg/ml. The median lethal dose in greater wax moth larvae (Galleria mellonella) was about 125mg/kg while the peptide caused no skin toxicity in a mouse model. A novel high-throughput luminescence assay was used to test peptide activity in infected G. mellonella, thus reducing vertebrate animal use. DGL13K killed P. aeruginosa in both the G. mellonella model and a mouse burn wound infection model, with bacterial viability 3-10-fold lower than in untreated controls. Future experiments will focus on optimizing peptide delivery, dose and frequency to further improve the antibacterial effect.",

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note = "Funding Information: SUG supported by the National Center for Advancing Translational Sciences of the National Institutes of Health Award Numbers grant UL1TR002494 and UL1 TR002377. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Additional support was provided from the Minnesota Partnership for Biotechnology and Medical Genomics through the Translational Product Development Fund (TPDF) and the University of Minnesota School of Dentistry, NIH.gov, www.dentistry.umn.edu. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We thank Lia Coicou, Brenda Koniar, Niki Larson, Margaret Mysz, and Beverly Norris from CTM for assistance with the mouse infection model and Austin McCullough, University of Minnesota School of Dentistry, for preliminary experiments with the G. mellonella model. Maria Giner Navalon is thanked for performing the HEK cell experiments as a visiting research student from the Universitat Internacional de Catalunya, Faculty of Dentistry, Barcelona, Spain. We thank Jennifer Nilson and Gary Dunny, Department of Microbiology and Immunology, University of Minnesota, for making the S. aureus strain USA300 LAC available for this research. Publisher Copyright: {\textcopyright} 2019 Gorr et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.",

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In vivo activity and low toxicity of the second-generation antimicrobial peptide DGL13K

Abstract

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PubMed: MeSH publication types

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