Vol.:(0123456789) 1 3 Amino Acids (2021) 53:1635–1648 https://doi.org/10.1007/s00726-021-03055-y ORIGINAL ARTICLE Antimicrobial peptidomes of Bothrops atrox and Bothrops jararacussu snake venoms Cleópatra Alves da Silva Caldeira 1,2,3  · Rafaela Diniz‑Sousa 1,3,4  · Daniel Carvalho Pimenta 5  · Ana Paula Azevedo dos Santos 3,6  · Carolina Bioni Garcia Teles 2,3,4,6  · Najla Benevides Matos 7  · Saulo Luís da Silva 8,9,10  · Rodrigo Guerino Stabeli 11,12  · Silvia Andrea Camperi 13,14  · Andreimar Martins Soares 1,2,3,4  · Leonardo de Azevedo Calderon 1,2,3,15 Received: 6 August 2020 / Accepted: 11 July 2021 / Published online: 4 September 2021 © The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature 2021 Abstract The worrisome emergence of pathogens resistant to conventional drugs has stimulated the search for new classes of antimi- crobial and antiparasitic agents from natural sources. Antimicrobial peptides (AMPs), acting through mechanisms that do not rely on the interaction with a specifc 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 Staphylococ- cus 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 purifed by combination of 3 kDa cut-of Amicon ®  ultracentrifugal flters and reverse-phase high-performance liquid chromatography, and then identifed by electrospray-ionization Ion-Trap/ Time-of-Flight mass spectrometry. Fourteen distinct peptides, with masses ranging from 443.17 to 1383.73 Da and primary structure between 3 and 13 amino acid residues, were sequenced. Among them, 13 contained unique sequences, including 4 novel bradykinin-potentiating-like peptides (BPPs), and a snake venom metalloproteinase tripeptide inhibitor (SVMPi). Although commonly found in Viperidae venoms, except for Bax-12, the BPPs and SVMPi here reported had not been described in B. atrox and B. jararacussu venoms. Among the novel peptides, some exhibited bactericidal activity towards P. aeruginosa and S. aureus, had low hemolytic efect, and were devoid of antiparasitic activity. The identifed novel antimi- crobial peptides may be relevant in the development of new drugs for the management of multidrug-resistant Gram-negative and Gram-positive bacteria. Keywords Snake venom peptidome · Bothrops atrox · Bothrops jararacussu · Peptidomics · Antimicrobial peptide Introduction Venoms represent evolutionary innovations that have evolved for predatory and defensive purposes independently in a broad phylogenetic range of animal lineages (Fry et al. 2009; Calvete 2017; Jenner and Undheim 2017). Venoms contain protein and peptide mixtures of varying complexity acting individually or as an integrated phenotype to wreak havoc on prey internal organs. Due to their high degree of target specifcity, the study of venom toxins is of growing interest for the pharmacological and biotechnological com- munities, as venoms are increasingly recognized as attractive subjects for chemical prospecting in the search of lead com- pounds for the development of novel biotechnological tools and biotherapeutics (King 2015). Venom components exhib- iting a range of pharmacologic activities, e.g., antihyperten- sive, analgesic, antitumoral, antiparasitic, and antimicrobial, have been reported (Samy et al. 2014; Almeida et al. 2016; Dal Mas et al. 2017; Akef 2018; Zhao et al. 2018; Sala et al. 2018). Scorpine is an antimicrobial peptide that exhibits Handling editor: J. Marshal. * Cleópatra Alves da Silva Caldeira cleopatra@unir.br; cleobiol@gmail.com * Leonardo de Azevedo Calderon calderon@unir.br Extended author information available on the last page of the article