PDF(Pubmed)
Abstract：
BACKGROUND: There is a global need to develop new therapies to treat infectious diseases and tackle the rise in antimicrobial resistance. To date, the larvae of the Black Solider Fly, Hermetia illucens, have the largest repertoire of antimicrobial peptides derived from insects. Antimicrobial peptides are of particular interest in the exploration of alternative antimicrobials due to their potent action and reduced propensity to induce resistance compared with more traditional antibiotics.
RESULTS: The predicted attacin from H. illucens, Hill_BB_C10074, was first identified in the transcriptome of H. illucens populations that had been fed a plant-oil based diet. In this study, recombinant Hill_BB_C10074 (500 µg/mL), was found to possess potent antimicrobial activity against the serious Gram-negative pathogen, Pseudomonas aeruginosa. Sequence and structural homology modelling predicted that Hill_BB_C10074 formed a homotrimeric complex that may form pores in the Gram-negative bacterial outer membrane. In vitro experiments defined the antimicrobial action of Hill_BB_C10074 against P. aeruginosa and transmission electron microscopy and electrochemical impedance spectroscopy confirmed the outer membrane disruptive power of Hill_BB_C10074 which was greater than the clinically relevant antibiotic, polymyxin B.
CONCLUSIONS: Combining predictive tools with in vitro approaches, we have characterised Hill_BB_C10074 as an important insect antimicrobial peptide and promising candidate for the future development of clinical antimicrobials.
RESULTS: The predicted attacin from H. illucens, Hill_BB_C10074, was first identified in the transcriptome of H. illucens populations that had been fed a plant-oil based diet. In this study, recombinant Hill_BB_C10074 (500 µg/mL), was found to possess potent antimicrobial activity against the serious Gram-negative pathogen, Pseudomonas aeruginosa. Sequence and structural homology modelling predicted that Hill_BB_C10074 formed a homotrimeric complex that may form pores in the Gram-negative bacterial outer membrane. In vitro experiments defined the antimicrobial action of Hill_BB_C10074 against P. aeruginosa and transmission electron microscopy and electrochemical impedance spectroscopy confirmed the outer membrane disruptive power of Hill_BB_C10074 which was greater than the clinically relevant antibiotic, polymyxin B.
CONCLUSIONS: Combining predictive tools with in vitro approaches, we have characterised Hill_BB_C10074 as an important insect antimicrobial peptide and promising candidate for the future development of clinical antimicrobials.
摘要：
背景：全球需要开发新的治疗感染性疾病的疗法，并应对抗菌素耐药性的上升。迄今为止,黑士兵蝇的幼虫,Hermetiaillucens,有来自昆虫的抗菌肽最大的库。抗微生物肽与更传统的抗生素相比，由于其有效的作用和降低的诱导抗性倾向，因此在探索替代抗微生物剂中特别感兴趣。
结果：来自H.illucens的预测attacin，Hill_BB_C10074首先在饲喂植物油基饮食的H.illucens种群的转录组中发现。在这项研究中,重组Hill_BB_C10074（500µg/mL），被发现对严重的革兰氏阴性病原体具有有效的抗菌活性，铜绿假单胞菌.序列和结构同源性建模预测，Hill_BB_C10074形成了同源三聚体复合物，该复合物可能在革兰氏阴性细菌外膜中形成孔。体外实验定义了Hill_BB_C10074对铜绿假单胞菌的抗菌作用，透射电子显微镜和电化学阻抗谱证实了Hill_BB_C10074的外膜破坏能力大于临床相关抗生素，多粘菌素B。
结论：将预测工具与体外方法相结合，我们已将Hill_BB_C10074鉴定为重要的昆虫抗菌肽，是未来临床抗菌药物开发的有希望的候选药物。
结果：来自H.illucens的预测attacin，Hill_BB_C10074首先在饲喂植物油基饮食的H.illucens种群的转录组中发现。在这项研究中,重组Hill_BB_C10074（500µg/mL），被发现对严重的革兰氏阴性病原体具有有效的抗菌活性，铜绿假单胞菌.序列和结构同源性建模预测，Hill_BB_C10074形成了同源三聚体复合物，该复合物可能在革兰氏阴性细菌外膜中形成孔。体外实验定义了Hill_BB_C10074对铜绿假单胞菌的抗菌作用，透射电子显微镜和电化学阻抗谱证实了Hill_BB_C10074的外膜破坏能力大于临床相关抗生素，多粘菌素B。
结论：将预测工具与体外方法相结合，我们已将Hill_BB_C10074鉴定为重要的昆虫抗菌肽，是未来临床抗菌药物开发的有希望的候选药物。
