Understanding the mechanism of action of peptide (p-BthTX-I) 2 derived from C-terminal region of phospholipase A2 (PLA 2 )-like bothropstoxin-I on Gram-positive and Gram-negative bacteria.

Autor: Santos-Filho NA; Instituto de Química, Universidade Estadual Paulista (UNESP), Araraquara, SP, Brazil; Campus Experimental de Registro, Universidade Estadual Paulista (UNESP), Araraquara, SP, Brazil; Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista (UNESP), Araraquara, SP, Brazil. Electronic address: norival.santos-filho@unesp.br., de Freitas LM; Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista (UNESP), Araraquara, SP, Brazil; Instituto de Química, Depto de Bioquímica, Universidade de São Paulo (USP), São Paulo, SP, Brazil., Santos CTD; Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista (UNESP), Araraquara, SP, Brazil., Piccoli JP; Instituto de Química, Universidade Estadual Paulista (UNESP), Araraquara, SP, Brazil., Fontana CR; Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista (UNESP), Araraquara, SP, Brazil., Fusco-Almeida AM; Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista (UNESP), Araraquara, SP, Brazil., Cilli EM; Instituto de Química, Universidade Estadual Paulista (UNESP), Araraquara, SP, Brazil. Electronic address: eduardo.cilli@unesp.br.
Jazyk: angličtina
Zdroj: Toxicon : official journal of the International Society on Toxinology [Toxicon] 2021 Jun; Vol. 196, pp. 44-55. Date of Electronic Publication: 2021 Mar 26.
DOI: 10.1016/j.toxicon.2021.03.015
Abstrakt: Based on the antimicrobial activity of bothropstoxin-I (BthTX-I) and on the premise that a C-terminal peptide of Lys49 myotoxin can reproduce the antimicrobial activity of the parent protein, we aimed to study the mechanism of action of a peptide derived from the C-terminal region of the myotoxin BthTX-I [(p-BthTX-I) 2 , sequence: KKYRYHLKPFCKK, disulfide-linked dimer] against Gram-positive and Gram-negative bacteria. Fluorescence quenching technique showed that the carboxyfluorescein labeled-peptide [CF-(p-BthTX-I) 2 ] when incubated with E. coli displayed a superior penetration activity than when incubated with S. aureus. Cell death induced by the peptide (p-BthTX-I) 2 showed a loss of membrane integrity in E. coli and S. aureus; however, the mechanisms of cell death were different, characterized by the presence of necrosis-like and apoptosis-like deaths, respectively. Scanning electron microscopy studies in E. coli and S. aureus showed morphological changes in the cells, with superficial deformities, appearance of wrinkles and bubbles, and formation of vesicles. Our results demonstrate that the mechanism of action of the peptide (p-BthTX-I) 2 is different in Gram-negative (E. coli) and Gram-positive (S. aureus) bacteria. Knowledge of the mechanism of action of these peptides is important, since they are promising prototypes for new antimicrobial drugs.
(Copyright © 2021 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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