Masadeh Majed, Ayyad Afnan, Haddad Razan, Alsaggar Mohammad, Alzoubi Karem, Alrabadi Nasr
Department of Pharmaceutical Technology, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid 22110, Jordan.
Department of Pharmacy Practice and Pharmacotherapeutics, University of Sharjah, Sharjah, UAE.
Curr Pharm Des. 2022;28(26):2177-2188. doi: 10.2174/1381612828666220705150817.
Managing bacterial infections caused by multidrug-resistant (MDR) and biofilmforming bacteria is a global health concern. Therefore, enormous efforts were directed toward finding potential alternative antimicrobial agents, such as antimicrobial peptides (AMPs).
We aimed to synthesize a novel modified hybrid peptide designed from natural parents' peptides with enhanced activity and reduced toxicity profile.
Rational design was used to hybridize the two antimicrobial peptides, in which the alpha-helical parts of BMAP-28 and LL-37 were combined. Then, several amino acid modifications were applied to generate a modified hybrid peptide named MAA-41. The physicochemical properties were checked using in silico methods. The MAA-41 was evaluated for its antimicrobial and anti-biofilm activities. Synergistic studies were performed with five conventional antibiotics. Finally, the cytotoxicity on mammalian cells and the hemolytic activity were assessed.
The MAA-41 revealed a broad-spectrum activity against Gram-positive and Gram-negative bacteria, including standard and MDR bacterial strains. The concentration against planktonic cells ranged between 10 and 20 μM, with higher potency against Gram-negative bacteria. The MAA-41 displayed potent activity in eradicating biofilm-forming cells, and the MBECs were equal to the MIC values reported for planktonic cells. This new peptide exhibited reduced toxicity profiles against erythrocyte cells but not against Vero cells. Combining MAA-41 peptides with conventional antibiotics improved the antimicrobial activity of the combined agents. Either synergistic or additive effects were shown as a significant decrease in MIC to 0.25 μM.
This study proposes the validity of a novel peptide (MAA-41) with enhanced antimicrobial activity and reduced toxicity, especially when used as conventional antibiotic combinations.
应对由多重耐药（MDR）和形成生物膜的细菌引起的细菌感染是一个全球健康问题。因此，人们付出了巨大努力来寻找潜在的替代抗菌剂，如抗菌肽（AMPs）。
我们旨在合成一种新型修饰杂合肽，该肽由天然亲本肽设计而成，具有增强的活性和降低的毒性。
采用合理设计将两种抗菌肽进行杂交，其中BMAP - 28和LL - 37的α - 螺旋部分相结合。然后，进行了若干氨基酸修饰以生成一种名为MAA - 41的修饰杂合肽。使用计算机模拟方法检查其理化性质。对MAA - 41的抗菌和抗生物膜活性进行评估。与五种传统抗生素进行协同研究。最后，评估其对哺乳动物细胞的细胞毒性和溶血活性。
MAA - 41对革兰氏阳性和革兰氏阴性细菌具有广谱活性，包括标准菌株和多重耐药菌株。对浮游细胞的作用浓度范围为10至20μM，对革兰氏阴性细菌的效力更高。MAA - 41在根除形成生物膜的细胞方面表现出强大活性，其最低生物被膜消除浓度（MBECs）与报道的浮游细胞最低抑菌浓度（MIC）值相当。这种新肽对红细胞的毒性降低，但对非洲绿猴肾细胞（Vero细胞）无此效果。将MAA - 41肽与传统抗生素联合使用可提高联合制剂的抗菌活性。协同或相加作用表现为MIC显著降低至0.25μM。
本研究提出了一种新型肽（MAA - 41）的有效性，该肽具有增强的抗菌活性和降低的毒性，特别是在用作传统抗生素组合时。
