Meucin-49, a multifunctional scorpion venom peptide with bactericidal synergy with neurotoxins
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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.
KeywordsCytotoxic peptide Hemotoxin Moonlighting protein Innate immunity Mesobuthus eupeus
Large conductance calcium-activated potassium channel
Human embryonic kidney
Half maximal lethal dose
- MALDI-TOF MS
Matrix-assisted laser desorption/ionization time of flight mass spectrometry
Methicillin-resistant coagulase-negative Staphylococci
Methicillin-resistant Staphylococcus aureus
Voltage-gated Na+ channel
Penicillin-resistant Staphylococcus aureus
Reversed-phase high-performance liquid chromatography
Scanning electron microscopy
Scorpion venom antimicrobial peptide
Scorpion venom classical antimicrobial peptide
Scorpion venom neurotoxin-type antimicrobial peptide
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.
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.
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).
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