In silico and in vitro characterization of the antibacterial effects of two novel synthetic peptides derived from TsAP-2

Abstract

Optimization of naturally occurring antimicrobial peptides (AMPs) seeks synthetic molecules that retain the positive characteristics of their native AMPs while presenting improved features. TsAP-2 is an AMP found in the venom gland of Tityus spp. scorpions, active against Gram-positive bacteria and Candida spp. yeasts. The analogs TsAP-A16 and TsAP-41 were designed by replacing neutral amino acids in TsAP-2 with positively charged ones, aiming to obtain peptides with broader action spectrum. In silico and in vitro methods employed in the characterization of the antibacterial activity of TsAP-A16 and TsAP-A41 revealed greater affinity for bacterial membranes than their native AMP, as well as bactericidal and antibiofilm action of both analogs against Gram-positive and Gram-negative strains. Associations with conventional antibiotics revealed synergistic and additive effects in individual combinations of TsAP-A16 and TsAP-A41 with gentamicin, penicillin and ceftazidime. Considering the accepted mechanism of action of AMPs relies on interactions with cell membranes, associations of AMPs with antimicrobial agents with intracellular targets demonstrates potential for rejuvenating widely-known drugs that have seen a decreased effectiveness due to antimicrobial resistance.