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Biological Profiling of Coleoptericins and Coleoptericin-Like Antimicrobial Peptides from the Invasive Harlequin Ladybird Harmonia axyridis

  • Rolf Hirsch
  • Jochen Wiesner
  • Alexander Marker
  • Armin Bauer
  • Peter E. Hammann
  • Andreas Vilcinskas
Chapter
Part of the Advances in Experimental Medicine and Biology book series

Abstract

The spread of antibiotic-resistant human pathogens and the declining number of novel antibiotics in the development pipeline is a global challenge that has fueled the demand for alternative options. The search for novel drug candidates has expanded to include not only antibiotics but also adjuvants capable of restoring antibiotic susceptibility in multidrug-resistant (MDR) pathogens. Insect-derived antimicrobial peptides (AMPs) can potentially fulfil both of these functions. We tested two coleoptericins and one coleoptericin-like peptides from the invasive harlequin ladybird Harmonia axyridis against a panel of human pathogens. The AMPs displayed little or no activity when tested alone but were active even against clinical MDR isolates of the Gram-negative ESKAPE strains when tested in combination with polymyxin derivatives, such as the reserve antibiotic colistin, at levels below the minimal inhibitory concentration. Assuming intracellular targets of the AMPs, our data indicate that colistin potentiates the activity of the AMPs. All three AMPs achieved good in vitro therapeutic indices and high intrahepatic stability but low plasma stability, suggesting they could be developed as adjuvants for topical delivery or administration by inhalation for anti-infective therapy to reduce the necessary dose of colistin (and thus its side effects) or to prevent development of colistin resistance in MDR pathogens.

Keywords

Anti-infectives Antimicrobial peptides Biological profiling Coleoptericin Harmonia axyridis 

Notes

Acknowledgments

We thank Dr. Yvonne Pfeifer for providing the multidrug-resistant clinical isolates from the strain library of the Robert Koch Institute in Wernigerode. We thank Kirsten-Susann Bommersheim, Sibylle Müller-Bertling, and Kirstin Ganske for excellent technical assistance and Dr. Richard M. Twyman for professional editing of the manuscript.

Conflict of Interest

The authors declare no conflict of interest.

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Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  • Rolf Hirsch
    • 1
    • 5
  • Jochen Wiesner
    • 4
  • Alexander Marker
    • 2
  • Armin Bauer
    • 2
  • Peter E. Hammann
    • 2
    • 5
  • Andreas Vilcinskas
    • 3
  1. 1.Fraunhofer Institute for Molecular Biology and Applied Ecology, Department of BioresourcesGiessenGermany
  2. 2.Sanofi-Aventis Deutschland GmbH, Industriepark HöchstFrankfurtGermany
  3. 3.Institute for Insect BiotechnologyJustus Liebig University of GießenGießenGermany
  4. 4.Fraunhofer Institute for Molecular Biology and Applied Ecology, Department of BioresourcesGiessenGermany
  5. 5.Present address: Evotec International GmbHHamburgGermany

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