Amino Acids

, Volume 50, Issue 8, pp 1025–1043 | Cite as

Meucin-49, a multifunctional scorpion venom peptide with bactericidal synergy with neurotoxins

  • Bin Gao
  • Julie Dalziel
  • Simone Tanzi
  • Shunyi Zhu
Original Article


Besides key roles in prey capture and predator defense, scorpion venom also functions as internal immune agents protecting the venom gland from infection and external immune agents cleaning saprophytic microbes from their own body surfaces. However, antimicrobials (typically antimicrobial peptides, AMPs) in the venom often exist in low abundance that might exclude their immune role alone, leaving an open question with regard to their in vivo biological function. Here, we report the bactericidal activity of seven peptides isolated from the scorpion Mesobuthus eupeus venom, including one classical α-helical AMP and five ion channel-targeted neurotoxins. This AMP of 49 amino acids (named Meucin-49) is a multifunctional molecule that displays a wide-spectrum and highly potent activity against Gram-positive and Gram-negative bacteria with strong hemotoxicity on scorpion’s predators (i.e., mammals, lizards, and birds) and high insecticidal activity. Although the neurotoxins targeting voltage-gated sodium (Nav) and/or large conductance calcium-activated potassium (BK) channels showed only marginal activity towards several species of bacteria, they were capable of significantly potentiating the bactericidal potency of Meucin-49. This observation highlights, for the first time, the venom’s antibacterial immune function mediated by a joint action between neurotoxins and AMPs. The findings that traditionally defined neurotoxins possess (synergistic) bactericidal activity, while the classical AMPs play predatory and defensive roles, provide new evidence in favor of a general and intrinsic multifunctionality of scorpion venom components.


Cytotoxic peptide Hemotoxin Moonlighting protein Innate immunity Mesobuthus eupeus 





Antimicrobial peptide


Large conductance calcium-activated potassium channel


Circular dichroism


Colony-forming unit




Human embryonic kidney


Half maximal lethal dose


Matrix-assisted laser desorption/ionization time of flight mass spectrometry




Methicillin-resistant coagulase-negative Staphylococci


Methicillin-resistant Staphylococcus aureus


Molecular weight


Voltage-gated Na+ channel


Neighbor joining


Propidium iodide


Penicillin-resistant Staphylococcus aureus


Reversed-phase high-performance liquid chromatography


Standard deviation


Standard error


Scanning electron microscopy


Scorpion venom antimicrobial peptide


Scorpion venom classical antimicrobial peptide


Scorpion venom neurotoxin-type antimicrobial peptide


Trifluoroacetic acid





We thank Prof. X. Qiu for providing Musca domestica, Prof. W. Du for providing lizard blood, and Dr. S. Finch for providing lolitrem B. This work was supported by the National Natural Science Foundation of China (31570773 and 31711530125) to S.Z. and the Danish Advanced Technology Foundation through the Advanced Technology Project PILOC (Grant no 061-2010-1) to S.T.

Author contributions

SZ conceived and designed this study and performed all sequence, structure, and evolutionary analyses. BG and SZ performed all the experiments except the work for the BK channel-blocking effect of MTβ-1 and MTβ-2 that was assayed by ST and JD, SZ, BG, and JD jointly wrote and reviewed the manuscript. All authors have seen this manuscript and agreed to submit it to Amino Acids.

Compliance with ethical standards

Conflict of interest

The authors declare that no competing interests exist.

Data archiving

The nucleotide sequences obtained in this study have been deposited in the GenBank database ( with accession numbers of ABR21064 (MTβ-1), ADT89767 (MTβ-2), and ADT64282 (MTβ-4).

Supplementary material

726_2018_2580_MOESM1_ESM.docx (2.4 mb)
Supplementary material 1 (DOCX 2480 kb)


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Copyright information

© Springer-Verlag GmbH Austria, part of Springer Nature 2018

Authors and Affiliations

  • Bin Gao
    • 1
  • Julie Dalziel
    • 2
  • Simone Tanzi
    • 2
    • 3
  • Shunyi Zhu
    • 1
  1. 1.Group of Peptide Biology and Evolution, State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of ZoologyChinese Academy of SciencesBeijingChina
  2. 2.Food Nutrition and Health Team, Food and Bio-based Products GroupAgResearchPalmerston NorthNew Zealand
  3. 3.Department of Micro- and NanotechnologyTechnical University of DenmarkKongens LyngbyDenmark

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