Peptidomimetic modification is a common route of optimization for biologically active peptides. Previous studies in our group have shown that conjugation of amphiphilic tobramycin to other antibacterials enhance their latent outer membrane permeabilizing and efflux blocking activity toward Gram-negative pathogens including Pseudomonas aeruginosa. Herein, we describe the antimicrobial adjuvant properties of amphiphilic lysine ligated to tobramycin. The most potent amphiphilic lysine-tobramycin conjugate 3 potentiated the antibacterial efficacy of 8 clinically used antibiotics against wild type, multidrug- and extensively drug-resistant P. aeruginosa isolates from Canadian hospitals whereas amphiphilic lysine 4 did not. Antibiotics that are synergistic with conjugate 3 included moxifloxacin, ciprofloxacin, erythromycin, chloramphenicol, trimethoprim, novobiocin, linezolid, and fosfomycin. Out of these 8 antibiotics, novobiocin showed highest synergy.

中文翻译：

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与妥布霉素缀合的两亲性赖氨酸可协同传统抗生素对抗野生型和多重耐药铜绿假单胞菌。


拟肽修饰是生物活性肽优化的常见途径。我们小组先前的研究表明，两亲性妥布霉素与其他抗菌药物的结合可增强其对包括铜绿假单胞菌在内的革兰氏阴性病原体的潜在外膜透化和外排阻断活性。在此，我们描述了与妥布霉素连接的两亲性赖氨酸的抗菌佐剂特性。最有效的两亲赖氨酸-妥布霉素缀合物 3 增强了 8 种临床使用的抗生素对来自加拿大医院的野生型、多药耐药和广泛耐药铜绿假单胞菌的抗菌功效，而两亲赖氨酸 4 则没有。与缀合物3具有协同作用的抗生素包括莫西沙星、环丙沙星、红霉素、氯霉素、甲氧苄啶、新生霉素、利奈唑胺和磷霉素。在这 8 种抗生素中，新生霉素表现出最高的协同作用。