Identification of an Antimicrobial Peptide from the Venom of the Trinidad Thick-Tailed Scorpion Tityus trinitatis with Potent Activity against ESKAPE Pathogens and Clostridioides difficile

Milena Mechkarska, Taylor Cunning, Megan Taggart, Nigel G Ternan, Jérôme Leprince, Laurent Coquet, Thierry Jouenne, Jordi Tena-Garcés, Juan Calvete, JM Conlon

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)
6 Downloads (Pure)

Abstract

Envenomation by the Trinidad thick-tailed scorpion Tityus trinitatis may result in fatal myocarditis and there is a high incidence of acute pancreatitis among survivors. Peptidomic analysis (reversed-phase HPLC followed by MALDI-TOF mass spectrometry and automated Edman degradation) of T. trinitatis venom led to the isolation and characterization of three peptides with antimicrobial activity. Their primary structures were established asTtAP-1 (FLGSLFSIGSKLLPGVFKLFSRKKQ.NH2), TtAP-2 (IFGMIPGLIGGLISAFK.NH2) and TtAP-3 (FFSLIPSLIGGLVSAIK.NH2). In addition, potassium channel and sodium channel toxins, present in the venom in high abundance, were identified by CID-MS/MS sequence analysis. TtAP-1 was the most potent against a range of clinically relevant Gram-positive and Gram-negative aerobes and against the anaerobe Clostridioides difficile (MIC = 3.1–12.5 µg/mL). At a concentration of 1× MIC, TtAP-1 produced rapid cell death (<15 min against Acinetobacter baumannii and Staphylococcus aureus). The therapeutic potential of TtAP-1 as an anti-infective agent is limited by its high hemolytic activity (LC50 = 18 µg/mL against mouse erythrocytes) but the peptide constitutes a template for the design of analogs that maintain the high bactericidal activity against ESKAPE pathogens but are less toxic to human cells. It is suggested that the antimicrobial peptides in the scorpion venom facilitate the action of the neurotoxins by increasing the membrane permeability of cells from either prey or predator.
Original languageEnglish
Article number1404
Pages (from-to)1-13
Number of pages13
JournalAntibiotics
Volume12
Issue number9
Early online date4 Sept 2023
DOIs
Publication statusPublished online - 4 Sept 2023

Bibliographical note

Funding Information:
This work was supported by The UWI Campus Research and Publication Fund (CRP.3.JUN20.07) and study and a travel grant from The UWI for visiting Ulster University awarded to M.M.

Publisher Copyright:
© 2023 by the authors.

Keywords

  • scorpion venom
  • ESKAPE pathogen
  • Clostridioides difficile
  • antimicrobial peptide
  • neurotoxin

Fingerprint

Dive into the research topics of 'Identification of an Antimicrobial Peptide from the Venom of the Trinidad Thick-Tailed Scorpion Tityus trinitatis with Potent Activity against ESKAPE Pathogens and Clostridioides difficile'. Together they form a unique fingerprint.

Cite this