Department of Science and Environment, Roskilde University, Roskilde, Denmark.
Section for Functional Genomics and Center for Bacterial Stress Response and Persistence, Department of Biology, University of Copenhagen, Copenhagen, Denmark.
Biopolymers. 2019 Jun;110(6):e23275. doi: 10.1002/bip.23275. Epub 2019 Apr 5.
Escherichia coli is the main etiological agent of urinary trait infections, able to form biofilms in indwelling devices, resulting in chronic infections which are refractory to antibiotics treatment. In this study, we investigated the antimicrobial and anti-biofilm properties exerted against E. coli ATCC 25922, by a set of peptoids and peptides modeled upon the peptide GN-2, previously reported as a valid antimicrobial agent. The putative antimicrobials were designed to evaluate the effect of cationicity, hydrophobicity and their partitioning on the overall properties against planktonic cells and biofilms as well as on LPS binding, permeabilization of Gram-negative bacteria membranes and hemolysis. The data demonstrated that peptides are stronger antimicrobials than the analogue peptoids which in return have superior anti-biofilm properties. In this study, we present evidence that peptides antimicrobial activity correlates with enhanced LPS binding and hydrophobicity but is not affected by partitioning. The data demonstrated that the enhanced anti-biofilm properties of the peptoids are associated with decreased hydrophobicity and increased penetration of the inner membrane, compared to that of their peptide counterpart, suggesting that the characteristic flexibility of peptoids or their lack of H-bonding donors in their backbone, would play a role in their ability to penetrate bacterial membranes.
大肠杆菌是尿路感染的主要病因，能够在留置装置中形成生物膜，导致对抗生素治疗产生抗性的慢性感染。在这项研究中，我们研究了一系列模仿先前报道的有效抗菌剂 GN-2 肽的肽和肽类似物对大肠杆菌 ATCC 25922 的抗菌和抗生物膜特性。这些假定的抗菌剂旨在评估正电性、疏水性及其分配对浮游细胞和生物膜以及 LPS 结合、革兰氏阴性细菌膜通透性和溶血的整体特性的影响。数据表明，肽比类似的肽类似物具有更强的抗菌活性，而肽类似物则具有更好的抗生物膜特性。在这项研究中，我们提供的证据表明，肽的抗菌活性与增强的 LPS 结合和疏水性相关，但不受分配的影响。数据表明，与肽对应物相比，肽类似物的抗生物膜特性增强与疏水性降低和内膜穿透性增加有关，这表明肽类似物的特征灵活性或其缺乏骨架中的氢键供体在穿透细菌膜的能力中发挥作用。
