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Bioevaluation of Ranatuerin-2Pb from the Frog Skin Secretion of Rana pipiens and Its Truncated Analogues

机译:从皮蛙蛙蛙皮肤分泌物及其截短的类似物对Ranatuerin-2Pb的生物评价

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摘要

Antimicrobial peptides (AMPs) are considered as a promising agent to overcome the drug-resistance of bacteria. Large numbers of AMPs have been identified from the skin secretion of Rana pipiens, including brevinins, ranatuerins, temporins and esculentins. In this study, the cDNA precursor of a broad-spectrum antimicrobial peptide, ranatuerin-2Pb, was cloned and identified. Additionally, two truncated analogues, RPa and RPb, were synthesised to investigate the structure-activity relationship of ranatuerin-2Pb. RPa lost antimicrobial activity against Candida albicans, MRSA, Enterococcus faecalis and Pseudomonas aeruginosa, while RPb retained its broad-spectrum antimicrobial activity. Additionally, ranatuerin-2Pb, RPa and RPb demonstrated inhibition and eradication effects against Staphylococcus aureus biofilm. RPb showed a rapid bacterial killing manner via membrane permeabilization without damaging the cell membrane of erythrocytes. Moreover, RPb decreased the mortality of S. aureus infected Galleria mellonella larvae. Collectively, our results suggested that RPb may pave a novel way for natural antimicrobial drug design.
机译:抗菌肽(AMPs)被认为是克服细菌耐药性的有前途的药物。从树蛙皮脂的皮肤分泌物中已经鉴定出大量的AMP,包括短纤维蛋白,毛豆素,临时蛋白和七叶皂苷。在这项研究中,克隆并鉴定了广谱抗菌肽ranatuerin-2Pb的cDNA前体。此外,合成了两个截短的类似物RPa和RPb,以研究ranatuerin-2Pb的结构-活性关系。 RPa对白色念珠菌,MRSA,粪肠球菌和铜绿假单胞菌失去了抗菌活性,而RPb保留了其广谱抗菌活性。此外,ranatuerin-2Pb,RPa和RPb对金黄色葡萄球菌生物膜具有抑制和根除作用。 RPb通过膜透化显示出快速的细菌杀伤方式,而不会破坏红细胞的细胞膜。此外,RPb降低了金黄色葡萄球菌感染的Malleria mellonella幼虫的死亡率。总的来说,我们的研究结果表明RPb可能为天然抗菌药物设计铺平了道路。

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