Venom and Biotherapeutics Molecules Lab., Medical Biotechnology Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran.
Venom and Biotherapeutics Molecules Lab., Medical Biotechnology Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran; Department of Microbiology, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, West Azerbaijan, Iran.
Microb Pathog. 2019 Feb;127:60-69. doi: 10.1016/j.micpath.2018.11.055. Epub 2018 Dec 1.
Bacterial infections caused by antibiotic resistant bacteria are the leading cause of morbidity and mortality after burn injuries. This issue has driven the need for promising antimicrobial drugs to eradication of bacterial pathogens. Accordingly, we aimed to determine the therapeutic value of melittin, as a natural Antimicrobial peptide (AMP), in eradication of extensively drug-resistant (XDR) Acinetobacter spp. on a mouse model of third degree burn infection. Melittin killed all examined XDR isolates at 4 μg/mL up to 3 h. Melittin caused significant fluorescence release from XDR isolates at the minimum dose of 0.062 μg/mL. Vesicle formation on the membrane and squeezing of bacteria followed by cell lysis indicated the membranolytic effect of melittin. Melittin at 32 μg/mL completely eradicated the colonized XDR bacteria on infected burn mice during 2 h. No toxicity was observed on injured or healthy derma, as well as circulating Red Blood Cells (RBCs) in the examined mice. Potent promising antibacterial activity of melittin and the lack of toxicity at the therapeutic dose can clarify that melittin can be implemented as a topical drug lead in a preclinical trial of third degree burn infections.
抗生素耐药菌引起的细菌感染是烧伤后发病率和死亡率的主要原因。这一问题促使人们需要有前途的抗菌药物来根除细菌病原体。因此，我们旨在确定蜂毒素作为一种天然抗菌肽 (AMP) 在消除广泛耐药 (XDR) 不动杆菌属。在三度烧伤感染的小鼠模型上。蜂毒素在 4μg/mL 时即可杀死所有检测到的 XDR 分离株，最高可达 3 小时。蜂毒素在 0.062μg/mL 的最低剂量下可导致 XDR 分离株显著荧光释放。膜上形成囊泡并挤压细菌，随后细胞裂解表明蜂毒素具有膜溶解作用。在 2 小时内，32μg/mL 的蜂毒素可完全清除感染烧伤小鼠上定植的 XDR 细菌。在检查的小鼠中，受伤或健康的真皮以及循环红细胞 (RBC) 均未观察到毒性。蜂毒素具有很强的有希望的抗菌活性，且在治疗剂量下无毒性，可以明确蜂毒素可以作为一种局部药物先导在三度烧伤感染的临床前试验中实施。
