Towards general and effective antifouling surfaces – covalent surface attachment of antimicrobial peptides

Abstract

<p>Healthcare-associated infections are of grave concern in healthcare facilities as these acquired infections pose a significant threat to the quality of life across the globe. Healthcare-associated infections are often related to the use of medical devices like catheters, joint prostheses, and implants. Medical devices are especially prone to bacterial growth, which can result in possible life-threatening complications. With the continued rise of antibiotic resistance, it is of utmost importance to minimize the numbers of medical device-associated infections induced by multidrug-resistant bacteria. Currently, there are prophylactic options in place to prevent biofilm-related infections, such as coating the medical devices with antibiotics or antiseptics. However, there are limitations to both antibiotics and antiseptics. These are not permanently incorporated into the medical device, causing the active ingredient to leak into the surrounding tissues and potentially increases the risk for acute hypersensitivity reactions and cytotoxicity, exacerbating the antibiotic-resistant problem and harming the environment with pollution. A promising class of antimicrobials that has the potential to evade the current problems are cationic antimicrobial peptides (AMPs), which can be permanently incorporated into medical devices. Due to their distinct characteristics, cationic AMPs can contribute to lessen the overall number of infection cases related to medical devices and reduce the need for potential treatment. <p>The presented project aimed to create a cationic AMP-coated surface material. The synthesized peptides were structurally distinctive with all peptide analogues having an azido group incorporated, which were to be covalently incorporated to alkyne-modified surfaces using the copper(I)-catalyzed azide-alkyne cycloaddition and had their ability to inhibit bacterial surface growth accessed. The peptides followed an RW-sequence with the intention of investigation the effects of lipophilicity modulation, PEGylation, cyclization, and surface density have against <i>Staphylococcus epidermidis</i> colonization on a pre-diced gold surface and a modified glass surface with gold nanoparticles. The bacterial response of <i>Escherichia coli</i> was also studied by subjecting the bacterium to a cationic AMP-coated glass surface.