Data_Sheet_1_Antimicrobial Activity of α-Peptide/β-Peptoid Lysine-Based Peptidomimetics Against Colistin-Resistant Pseudomonas aeruginosa Isolated From Cystic Fibrosis Patients.PDF

Pseudomonas aeruginosa infection is a predominant cause of morbidity and mortality in patients with cystic fibrosis infection and with a compromised immune system. Emergence of bacterial resistance renders existing antibiotics inefficient, and therefore discovery of new antimicrobial agents is highly warranted. In recent years, numerous studies have demonstrated that antimicrobial peptides (AMPs) constitute potent agents against a range of pathogenic bacteria. However, AMPs possess a number of drawbacks such as susceptibility to proteolytic degradation with ensuing low bioavailability. To circumvent these undesired properties of AMPs unnatural amino acids or altered backbones have been incorporated to provide stable peptidomimetics with retained antibacterial activity. Here, we report on antimicrobial α-peptide/β-peptoid lysine-based peptidomimetics that exhibit high potency against clinical drug-resistant P. aeruginosa strains obtained from cystic fibrosis patients. These clinical strains possess phoQ and/or pmrB mutations that confer high resistance to colistin, the last-resort antibiotic for treatment of infections caused by P. aeruginosa. The lead peptidomimetic LBP-2 demonstrated a 12-fold improved anti-pseudomonal activity as compared to colistin sulfate as well as favorable killing kinetics, similar antibiofilm activity, and moderate cytotoxicity.

铜绿假单胞菌（Pseudomonas aeruginosa）感染是囊性纤维化患者以及免疫功能受损人群发病与死亡的主要诱因。细菌耐药性的出现使得现有抗生素的抗菌效能大幅下降，因此亟需开发新型抗菌制剂。近年来，大量研究证实抗菌肽（antimicrobial peptides, AMPs）是对抗多种致病细菌的强效制剂。但抗菌肽存在诸多缺陷，例如易被蛋白酶降解，进而导致生物利用度较低。为规避抗菌肽的这些不良特性，研究人员已引入非天然氨基酸或修饰其骨架，以获得保留抗菌活性的稳定肽模拟物。本研究报道了一类基于赖氨酸的α-肽/β-肽拟肽类抗菌剂，其对从囊性纤维化患者体内分离得到的临床耐药铜绿假单胞菌菌株展现出强效抗菌活性。这些临床菌株携带phoQ和/或pmrB基因突变，可对多粘菌素——治疗铜绿假单胞菌感染的最后一线抗生素——产生高度耐药性。先导肽模拟物LBP-2相较于硫酸多粘菌素，抗铜绿假单胞菌活性提升了12倍，同时具备优良的杀菌动力学特性、相似的抗生物膜活性，且细胞毒性适中。