Scorpion; Tityus stigmurus; Peptide; Antibacterial; antibiofilm; Wound healing
Microbial infections are a serious public health problem with high morbimortality worldwide that, combined with the rapid emergence of microorganisms resistant to conventional antimicrobials, has boosting the search for new antibiotic agents in different natural sources. In this context, antimicrobial peptides without disulfide bridges are molecules with multiple biological activities, with high potential pharmacological. TsAP-2 is a peptide without disulfide bridges from Tityus stigmurus scorpion with antiproliferative, antifungal and antibacterial effect reported in the literature. In this study, we focused on evaluating the antibacterial activity, antibiofilm and the effect of the combination of TsAP-2 with conventional antibiotics in vitro, also investigating its antimicrobial action in the skin wound model infected by Staphylococcus aureus and microbial activity in Galleria mellonela larvae infected with multidrug-resistant S. aureus. TsAP-2 revealed a broad-spectrum antibacterial activity in vitro, with antimicrobial and antibiofilm action against standard and multidrug-resistant strains of S. aureus with greater effect on early biofilm. TsAP-2 also showed additive and synergistic effects in 50% of associations with conventional antibiotics, especially with β-lactam drugs and cefoxitin. In addition, TsAP-2 showed antibacterial and healing action in vivo, reducing the area and the necrosis of the surgical wound infected by S. aureus, and promoted an increase in neovascularization and epithelialization in the skin wound. TsAP-2 also reduced by 50% the resistant bacteria circulating in the hemolymph of G. mellonela larvae, promoting an increase in their survival, with absence of toxic signs on the uninfected insect. Taken together, this approach highlights the wide pharmacological potential of TsAP-2, making it an attractive molecule for prospecting for new drugs with applicability in anti-infective therapy.