Identification of the molecular determinants of the antibacterial activity of LmutTX, a Lys49 phospholipase A2 homologue isolated from Lachesis muta muta snake venom (Linnaeus, 1766)


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Article
Language
English
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Abstract
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 The primary structure made it possible to identify an unpublished protein from L. m. muta venom, named LmutTX, that presented high identity with other Lys49 PLA(2)s from bothropic venoms. Synthetic peptides designed from LmutTX were evaluated for their cytotoxic and antimicrobial activities. LmutTX was cytotoxic against C2C12 myotubes at concentrations of at least 200 g/mL, whereas the peptides showed a low cytolytic effect. LmutTX showed antibacterial activity against Gram-positive and Gram-negative bacteria; however, S. aureusATCC 29213 and MRSA strains were more sensitive to the toxin's action. Synthetic peptides were tested on S. aureus, MRSA and P. aeruginosaATCC 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.
Reference
Diniz-Sousa R, Caldeira CA.S., Kayano AM., Paloschi MV., Pimenta DC, Simões-Silva R, et al. Identification of the molecular determinants of the antibacterial activity of LmutTX, a Lys49 phospholipase A2 homologue isolated from Lachesis muta muta snake venom (Linnaeus, 1766). Basic Clin Pharmacol Toxicol. 2018 Apr;122(4):413-23.. doi:10.1111/bcpt.12921.
Link to cite this reference
https://repositorio.butantan.gov.br/handle/butantan/2397
Issue Date
2018


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