Antimicrobial peptidomes of Bothrops atrox and Bothrops jararacussu snake venoms

C.A. DA S. CALDEIRA; R. DINIZ-SOUSA; D. CARVALHO PIMENTA; A. P. AZEVEDO DOS SANTOS; C. BIONI GARCIA TELES ; N. BENEVIDES MATOS; R. GUERINO STABELI; S. A. CAMPERI; A. MARTINS SOARES; L. DE AZEVEDO CALDERON

AMINO ACIDS

SPRINGER

Lugar: Berlin; Año: 2021

0939-4451

The worrisome emergence of pathogens resistant to conventional drugs has stimulated the search for new classes of antimicrobial and antiparasitic agents from natural sources. Antimicrobial peptides (AMPs), acting through mechanisms that do not rely on the interaction with a specific receptor, provide new possibilities for the development of drugs against resistant organisms. This study sought to purify and proteomically characterize the antimicrobial and antiparasitic peptidomes of B. atrox and B. jararacussu snake venoms against Gram-positive (Staphylococcus aureus, Methicillin-resistant Staphylococcus aureus- MRSA), Gram-negative (Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae) bacteria, and the protozoan parasites Leishmania amazonensis and Plasmodium falciparum (clone W2, resistant to chloroquine). To this end, B. atrox and B. jararacussu venom peptides were purified by combination of 3 kDa cut-off Amicon® ultracentrifugal filters and reverse-phase high-performance liquid chromatography, and then identified by electrospray-ionization Ion Trap/Time-of-Flight mass spectrometry. Fifteen peptides, with masses ranging from 443.17 to 1383.73 Da and primary structure between 3 to 13 amino acid residues, were sequenced. Among them, 13 contained unique sequences, including 5 novel bradykinin-potentiating-like peptides (BBPs) and 2 metalloproteinase inhibitors SVMPi), which although commonly found in Viperidae venoms had not been described yet in B. atrox and B. jararacussu. Among the novel peptides, some exhibited bactericidal activity towards, P. aeruginosa and S. aureus, had low hemolytic effect, and were devoid of antiparasitic activity. The identified novel antimicrobial peptides may be relevant in the development of new drugs for the management of multidrug-resistant Gram-negative and Gram-positive bacteria.