Laboratório de Purificação de Proteínas e suas Funções Biológicas, FACFAN, Universidade Federal de Mato Grosso do Sul, Campo Grande, Brazil.
Instituto de Química, Departamento de Bioquímica e Química Tecnológica, Universidade Estadual Paulista Júlio de Mesquita Filho, Araraquara, Brazil.
Biochim Biophys Acta Gen Subj. 2022 Dec;1866(12):130244. doi: 10.1016/j.bbagen.2022.130244. Epub 2022 Sep 23.
Antimicrobial peptides (AMPs) are promising tools for developing new antibiotics. We described the design of IKR18, an AMP designed with the aid of computational tools. IKR18 showed antimicrobial activity against Gram-negative and Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). CD studies revealed that IKR18 assumes an alpha-helical structure in the membrane-mimetic environment. The action mechanism IKR18 involves damage to the bacteria membrane, as demonstrated by Sytox green uptake. Furthermore, IKR18 displayed synergic and additive effects in combination with antibiotics ciprofloxacin and vancomycin. The peptide showed anti-biofilm activity in concentration and efficiency compared with commercial antibiotics, involving the direct death of bacteria, as confirmed by scanning electron microscopy. The anti-infective activity of IKR18 was demonstrated in the Galleria mellonella model infected with S. aureus, MRSA, and Acinetobacter baumannii. The novel bioinspired peptide, IKR18, proved to be effective in the control of bacterial infection, opening opportunities for the development of further assays, including preclinical models.
抗菌肽 (AMPs) 是开发新型抗生素的有前途的工具。我们描述了 IKR18 的设计,这是一种在计算工具辅助下设计的 AMP。IKR18 对革兰氏阴性和革兰氏阳性细菌具有抗菌活性,包括耐甲氧西林金黄色葡萄球菌 (MRSA)。CD 研究表明,IKR18 在模拟膜的环境中呈现出 α-螺旋结构。IKR18 的作用机制涉及细菌膜的损伤,如 Sytox green 摄取所证明的那样。此外,IKR18 与抗生素环丙沙星和万古霉素联合使用具有协同和相加作用。与商业抗生素相比,该肽在浓度和效率上均显示出抗生物膜活性,通过扫描电子显微镜证实了其涉及细菌的直接死亡。IKR18 在感染金黄色葡萄球菌、MRSA 和鲍曼不动杆菌的家蚕模型中表现出抗感染活性。新型仿生肽 IKR18 被证明可有效控制细菌感染,为进一步的检测,包括临床前模型的开发提供了机会。