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 .

Autor: Mechkarska M; Department of Life Sciences, Faculty of Science and Technology, St. Augustine Campus, The University of The West Indies, St. Augustine, Trinidad and Tobago., Cunning TS; Nutrition Innovation Centre for Food and Health (NICHE), School of Biomedical Sciences, Ulster University, Coleraine BT52 1SA, UK., Taggart MG; Nutrition Innovation Centre for Food and Health (NICHE), School of Biomedical Sciences, Ulster University, Coleraine BT52 1SA, UK., Ternan NG; Nutrition Innovation Centre for Food and Health (NICHE), School of Biomedical Sciences, Ulster University, Coleraine BT52 1SA, UK., Leprince J; Université Rouen Normandie, INSERM, NorDiC UMR 1239, HeRacLeS, US 51, PRIMACEN, F-76000 Rouen, France., Coquet L; Université Rouen Normandie, INSA Rouen Normandie, CNRS, PBS UMR 6270, HeRacLeS US 51 UAR 2026 PISSARO, F-76000 Rouen, France., Jouenne T; Université Rouen Normandie, INSA Rouen Normandie, CNRS, PBS UMR 6270, HeRacLeS US 51 UAR 2026 PISSARO, F-76000 Rouen, France., Tena-Garcés J; Evolutionary and Translational Venomics Laboratory, Consejo Superior de Investigaciones Científicas (CSIC), 46010 Valencia, Spain., Calvete JJ; Evolutionary and Translational Venomics Laboratory, Consejo Superior de Investigaciones Científicas (CSIC), 46010 Valencia, Spain., Conlon JM; Diabetes Research Centre, School of Biomedical Sciences, Ulster University, Coleraine BT52 1SA, UK.
Jazyk: angličtina
Zdroj: Antibiotics (Basel, Switzerland) [Antibiotics (Basel)] 2023 Sep 04; Vol. 12 (9). Date of Electronic Publication: 2023 Sep 04.
DOI: 10.3390/antibiotics12091404
Abstrakt: 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 (LC 50 = 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.
Databáze: MEDLINE
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