Daniele-Silva Alessandra, Fernandes Janainna Xavier, Parente Adriana Marina E Silva, Amorim-Carmo Bruno, Rodrigues Suedson de Carvalho Silva, Sousa Lucas Hilário Nogueira de, Dos Santos Elizabeth C G, de Carvalho Thaís G, Araújo Júnior Raimundo F, Mendes Raudiney Frankilin Vasconcelos, Ximenes Rafael Matos, da Silva-Júnior Arnóbio A, Soares Luiz Alberto Lira, Araújo Renata Mendonça, Fernandes-Pedrosa Matheus F
Programa de Pós-Graduação em Desenvolvimento e Inovação Tecnológica em Medicamentos, Universidade Federal do Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil.
Programa de Pós-Graduação em Ciências Farmacêuticas, Laboratório de Tecnologia e Biotecnologia Farmacêutica, Departamento de Farmácia, Universidade Federal do Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil.
Biochimie. 2025 Jul 23. doi: 10.1016/j.biochi.2025.07.023.
Microbial infections are a public health problem that combined with the emergence of resistant microorganisms have boosted the search for new antibiotic agents. In this approach, the antibacterial and antibiofilm effects in vitro of TsAP-2 (peptide from the Tityus stigmurus scorpion venom) were evaluated. In addition, its antimicrobial action in the skin wound model infected with Staphylococcus aureus and Galleria mellonella larvae infected with a multidrug-resistant strain and the effect of the combination with conventional antibiotics in vitro were investigated. TsAP-2 demonstrated broad-spectrum antibacterial activity in vitro, with antibiofilm action against standard and multidrug-resistant strains during early biofilm formation. Furthermore, TsAP-2 exhibited additive and synergistic effects when combined with conventional antibiotics. TsAP-2 revealed antibacterial and healing activity in vivo, reducing wound area and necrosis, while promoting an increase in neovascularization and epithelialization. TsAP-2 decreased the number of resistant bacteria in infected larvae, increasing their survival rate. The structural conformation of the peptide was assessed using circular dichroism and its three-dimensional structure was determined through NMR spectroscopy. In zwitterionic vesicles, TsAP-2 revealed a random conformation and a predominant helical structure in the presence of anionic vesicles. The three-dimensional structure of TsAP-2 obtained by NMR analysis indicates a helical segment from the 7th to the 15th residue, with flexibility in the N and C-terminal peptide domains. Taken together, this approach indicates the ability of TsAP-2 to change its conformation when interacting with biomimetic medium, highlights its extensive pharmacological potential, being an attractive candidate for the exploration of new anti-infective drugs.
微生物感染是一个公共卫生问题，加之耐药微生物的出现，推动了新型抗生素药物的研发。在本研究中，评估了TsAP-2（一种来自巴西金幽灵蝎毒液的肽）的体外抗菌和抗生物膜作用。此外，还研究了其在金黄色葡萄球菌感染的皮肤伤口模型和多重耐药菌株感染的大蜡螟幼虫中的抗菌作用，以及与传统抗生素联合使用的体外效果。TsAP-2在体外表现出广谱抗菌活性，在生物膜形成早期对标准菌株和多重耐药菌株具有抗生物膜作用。此外，TsAP-2与传统抗生素联合使用时表现出相加和协同作用。TsAP-2在体内显示出抗菌和愈合活性，可减少伤口面积和坏死，同时促进新血管形成和上皮形成增加。TsAP-2减少了感染幼虫中的耐药菌数量，提高了它们的存活率。使用圆二色性评估了该肽的结构构象，并通过核磁共振光谱确定了其三维结构。在两性离子囊泡中，TsAP-2呈现随机构象，而在阴离子囊泡存在下则呈现主要的螺旋结构。通过核磁共振分析获得的TsAP-2三维结构表明，从第7个残基到第15个残基存在一个螺旋片段，肽的N端和C端结构域具有灵活性。综上所述，该研究表明TsAP-2在与仿生介质相互作用时能够改变其构象，突出了其广泛的药理潜力，是探索新型抗感染药物的有吸引力的候选物。
