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

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Advances in Microbiology, Infectious Diseases and Public Health

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.

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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.

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The authors declare no conflict of interest.

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Correspondence to Andreas Vilcinskas .

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Appendix

Appendix

Table S1 Overview of the test strains and their culture conditions
Table S2 Activity of the H. axyridis AMPs against reference strains

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Hirsch, R., Wiesner, J., Marker, A., Bauer, A., Hammann, P.E., Vilcinskas, A. (2018). Biological Profiling of Coleoptericins and Coleoptericin-Like Antimicrobial Peptides from the Invasive Harlequin Ladybird Harmonia axyridis . In: Donelli, G. (eds) Advances in Microbiology, Infectious Diseases and Public Health. Advances in Experimental Medicine and Biology(), vol 1214. Springer, Cham. https://doi.org/10.1007/5584_2018_276

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