Department of Nutrition, Henry Fok School of Food Science and Engineering, Shaoguan University, Shaoguan 512005, China.
Natural Drug Discovery Group, School of Pharmacy, Queen's University, Belfast BT9 7BL, Northern Ireland, UK.
Biomolecules. 2019 Jun 25;9(6):249. doi: 10.3390/biom9060249.
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 R, 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 biofilm. RPb showed a rapid bacterial killing manner via membrane permeabilization without damaging the cell membrane of erythrocytes. Moreover, RPb decreased the mortality of infected larvae. Collectively, our results suggested that RPb may pave a novel way for natural antimicrobial drug design.
抗菌肽(AMPs)被认为是克服细菌耐药性的一种有前途的药物。从 R 的皮肤分泌物中已经鉴定出大量的 AMPs,包括 brevinins、ranatuerins、temporins 和 esculentins。在这项研究中,克隆并鉴定了一种广谱抗菌肽 ranatuerin-2Pb 的 cDNA 前体。此外,还合成了两种截断类似物 RPa 和 RPb,以研究 ranatuerin-2Pb 的结构-活性关系。RPa 丧失了对白色念珠菌、耐甲氧西林金黄色葡萄球菌、粪肠球菌和铜绿假单胞菌的抗菌活性,而 RPb 保留了其广谱抗菌活性。此外,ranatuerin-2Pb、RPa 和 RPb 对生物膜表现出抑制和清除作用。RPb 通过破坏细胞膜使红细胞在没有损伤细胞膜的情况下快速杀菌。此外,RPb 降低了 感染 幼虫的死亡率。总之,我们的结果表明,RPb 可能为天然抗菌药物设计开辟一条新途径。