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Identification of the Molecular Determinants of the Antibacterial Activity of Lmut TX , a Lys49 Phospholipase A 2 Homologue Isolated from Lachesis muta muta Snake Venom (Linnaeus, 1766)
Author(s) -
DinizSousa Rafaela,
Caldeira Cleópatra A. S.,
Kayano Anderson M.,
Paloschi Mauro V.,
Pimenta Daniel. C.,
SimõesSilva Rodrigo,
Ferreira Amália S.,
Zanchi Fernando B.,
Matos Najla B.,
Grabner Fernando P.,
Calderon Leonardo A.,
Zuliani Juliana P.,
Soares Andreimar M.
Publication year - 2018
Publication title -
basic and clinical pharmacology and toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.805
H-Index - 90
eISSN - 1742-7843
pISSN - 1742-7835
DOI - 10.1111/bcpt.12921
Subject(s) - venom , snake venom , biology , bothrops , microbiology and biotechnology , biochemistry , phospholipase a , phospholipase a2 , enzyme
Snake venom phospholipases A 2 ( PLA 2 s) are responsible for numerous pathophysiological effects in snakebites; however, their biochemical properties favour antimicrobial actions against different pathogens, thus constituting a true source of potential microbicidal agents. This study describes the isolation of a Lys49 PLA 2 homologue from Lachesis muta muta venom using two chromatographic steps: size exclusion and reverse phase. The protein showed a molecular mass of 13,889 Da and was devoid of phospholipase activity on an artificial substrate. The primary structure made it possible to identify an unpublished protein from L. m. muta venom, named Lmut TX , that presented high identity with other Lys49 PLA 2 s from bothropic venoms. Synthetic peptides designed from Lmut TX were evaluated for their cytotoxic and antimicrobial activities. Lmut TX was cytotoxic against C2C12 myotubes at concentrations of at least 200 μg/mL, whereas the peptides showed a low cytolytic effect. Lmut TX showed antibacterial activity against Gram‐positive and Gram‐negative bacteria; however, S. aureus ATCC 29213 and MRSA strains were more sensitive to the toxin's action. Synthetic peptides were tested on S. aureus , MRSA and P. aeruginosa ATCC 27853 strains, showing promising results. This study describes for the first time the isolation of a Lys49 PLA 2 from Lachesis snake venom and shows that peptides from specific regions of the sequence may constitute new sources of molecules with biotechnological potential.