Amino Acids

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

Original Article
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Abstract

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.

Keywords

Cytotoxic peptide Hemotoxin Moonlighting protein Innate immunity Mesobuthus eupeus 

Abbreviations

3D

Three-dimensional

AMP

Antimicrobial peptide

BK

Large conductance calcium-activated potassium channel

CD

Circular dichroism

CFU

Colony-forming unit

DMSO

Dimethylsulfoxide

HEK

Human embryonic kidney

LD50

Half maximal lethal dose

MALDI-TOF MS

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

Met

Methionine

MRCNS

Methicillin-resistant coagulase-negative Staphylococci

MRSA

Methicillin-resistant Staphylococcus aureus

MW

Molecular weight

Nav

Voltage-gated Na+ channel

NJ

Neighbor joining

PI

Propidium iodide

PRSA

Penicillin-resistant Staphylococcus aureus

RP-HPLC

Reversed-phase high-performance liquid chromatography

SD

Standard deviation

SE

Standard error

SEM

Scanning electron microscopy

svAMP

Scorpion venom antimicrobial peptide

svcAMP

Scorpion venom classical antimicrobial peptide

svntAMP

Scorpion venom neurotoxin-type antimicrobial peptide

TFA

Trifluoroacetic acid

TFE

Trifluoroethanol

Notes

Acknowledgements

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 (http://www.ncbi.nlm.nih.gov/) 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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