1. Rapid Assembly of Infection-Resistant Coatings: Screening and Identification of Antimicrobial Peptides Works in Cooperation with an Antifouling Background.
- Author
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Yu K, Alzahrani A, Khoddami S, Cheng JTJ, Mei Y, Gill A, Luo HD, Haney EF, Hilpert K, Hancock REW, Lange D, and Kizhakkedathu JN
- Subjects
- Acrylamides chemistry, Animals, Anti-Bacterial Agents chemical synthesis, Antimicrobial Cationic Peptides chemical synthesis, Catheters microbiology, Coated Materials, Biocompatible chemical synthesis, Humans, Immobilized Proteins chemical synthesis, Indoles chemistry, Male, Mice, Inbred BALB C, Polymers chemistry, Pseudomonas aeruginosa drug effects, Pseudomonas aeruginosa physiology, Staphylococcus saprophyticus drug effects, Staphylococcus saprophyticus physiology, Urinary Tract Infections prevention & control, Mice, Anti-Bacterial Agents pharmacology, Antimicrobial Cationic Peptides pharmacology, Biofouling prevention & control, Coated Materials, Biocompatible pharmacology, Immobilized Proteins pharmacology
- Abstract
Bacterial adhesion and the succeeding biofilm formation onto surfaces are responsible for implant- and device-associated infections. Bifunctional coatings integrating both nonfouling components and antimicrobial peptides (AMPs) are a promising approach to develop potent antibiofilm coatings. However, the current approaches and chemistry for such coatings are time-consuming and dependent on substrates and involve a multistep process. Also, the information is limited on the influence of the coating structure or its components on the antibiofilm activity of such AMP-based coatings. Here, we report a new strategy to rapidly assemble a stable, potent, and substrate-independent AMP-based antibiofilm coating in a nonfouling background. The coating structure allowed for the screening of AMPs in a relevant nonfouling background to identify optimal peptide combinations that work in cooperation to generate potent antibiofilm activity. The structure of the coating was changed by altering the organization of the hydrophilic polymer chains within the coatings. The coatings were thoroughly characterized using various surface analytical techniques and correlated with the efficiency to prevent biofilm formation against diverse bacteria. The coating method that allowed the conjugation of AMPs without altering the steric protection ability of hydrophilic polymer structure results in a bifunctional surface coating with excellent antibiofilm activity. In contrast, the conjugation of AMPs directly to the hydrophilic polymer chains resulted in a surface with poor antibiofilm activity and increased adhesion of bacteria. Using this coating approach, we further established a new screening method and identified a set of potent surface-tethered AMPs with high activity. The success of this new peptide screening and coating method is demonstrated using a clinically relevant mouse infection model to prevent catheter-associated urinary tract infection (CAUTI).
- Published
- 2021
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