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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| Authors: | Rafaela Diniz‐Sousa Cleópatra A S Caldeira Anderson M Kayano Mauro V Paloschi Daniel C Pimenta Rodrigo Simões‐Silva Amália S Ferreira Fernando B Zanchi Najla B Matos Fernando P Grabner Leonardo A Calderon Juliana P Zuliani Andreimar M Soares |
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| Affiliation: | 1. Center for the Study of Biomolecules Applied to Heath (CEBio), Oswaldo Cruz Foundation (FIOCRUZ), Fiocruz Rondonia, RO, Brazil;2. Medicine Department, Federal University of Rondonia (UNIR), RO, Brazil;3. Experimental Biology Posgraduate Program (PGBIOEXP), Federal University of Rondonia (UNIR), Porto Velho, RO, Brazil;4. Biodiversity and Biotechnology Posgraduate Program, Rede BIONORTE, Manaus, Brazil;5. Laboratory of Cellular Immunology Applied to Heath, Oswaldo Cruz Foundation (FIOCRUZ), Fiocruz Rondonia, Porto Velho, RO, Brazil;6. Biochemistry and Biophysics Laboratory, Butantan Institute, Sao Paulo, SP, Brazil;7. Microbiology Laboratory, Research Center on Tropical Medicine of Rondonia (CEPEM), Porto Velho, RO, Brazil;8. Oswaldo Cruz Foundation (FIOCRUZ), Fiocruz Rondonia, Porto Velho, RO, Brazil;9. Sao Lucas Universitary Center (UNISL), Porto Velho, RO, Brazil |
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| Abstract: | Snake venom phospholipases A2 (PLA2s) 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 PLA2 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 The primary structure made it possible to identify an unpublished protein from L. m. muta venom, named LmutTX, that presented high identity with other Lys49 PLA2s from bothropic venoms.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 μg/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 PLA2 from Lachesis snake venom and shows that peptides from specific regions of the sequence may constitute new sources of molecules with biotechnological potential. |
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