Akhash Nasim, Farajzadeh Sheikh Ahmad, Farshadzadeh Zahra
Health Research Institute, Infectious and Tropical Diseases Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
Department of Microbiology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
Sci Rep. 2024 Jan 26;14(1):2256. doi: 10.1038/s41598-024-52721-0.
Nowadays, antimicrobial peptides are promising to confront the existing global crisis of antibiotic resistance. Here, a novel analogue peptide (mKLK) was designed based upon a D-form amidated sapecin B-derived peptide (KLK) by replacing two lysine residues with two tryptophan and one leucine by lysine, and inserting one alanine. The mKLK displayed superior amphipathic helixes in which the most of hydrophobic residues are confined to one face of the helix and had a higher hydrophobic moment compared with KLK. The mKLK retained its antibacterial activity and structure in human serum, suggesting its stability to proteolytic degradation. The values of MIC and MBC for mKLK were equal to those of KLK against clinical strains of methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-susceptible Staphylococcus aureus (MSSA). However, mKLK showed more capability of in vitro inhibiting, eradicating, and dispersing MRSA and MSSA biofilms compared with KLK. Furthermore, a remarkable inhibitory activity of mKLK against MRSA and MSSA biofilms was seen in the murine model of catheter-associated biofilm infection. Results of this study show that mKLK not only exhibits antibacterial activity and serum stability but also a potent biofilm inhibitory activity at sub-MIC concentrations, confirming its potential therapeutic advantage for preventing biofilm-associated MRSA and MSSA infections.
如今，抗菌肽有望应对现有的全球抗生素耐药危机。在此，基于D型酰胺化的沙贝辛B衍生肽（KLK）设计了一种新型类似物肽（mKLK），用两个色氨酸取代两个赖氨酸残基，并用赖氨酸取代一个亮氨酸，并插入一个丙氨酸。mKLK表现出优异的两亲性螺旋结构，其中大多数疏水残基集中在螺旋的一侧，与KLK相比具有更高的疏水矩。mKLK在人血清中保留了其抗菌活性和结构，表明其对蛋白水解降解具有稳定性。mKLK对耐甲氧西林金黄色葡萄球菌（MRSA）和甲氧西林敏感金黄色葡萄球菌（MSSA）临床菌株的MIC和MBC值与KLK相当。然而，与KLK相比，mKLK在体外抑制、根除和分散MRSA和MSSA生物膜方面表现出更强的能力。此外，在导管相关生物膜感染的小鼠模型中，观察到mKLK对MRSA和MSSA生物膜具有显著的抑制活性。本研究结果表明，mKLK不仅具有抗菌活性和血清稳定性，而且在亚MIC浓度下具有强大的生物膜抑制活性，证实了其在预防生物膜相关的MRSA和MSSA感染方面的潜在治疗优势。
