Abstract
Medical devices with an effective anti-colonization surface are important tools for combatting healthcare-associated infections. Here, we investigated the anti-colonization efficacy of antimicrobial peptides covalently attached to a gold model surface. The gold surface was modified by a self-assembled polyethylene glycol monolayer with an acetylene terminus. The peptides were covalently connected to the surface through a copper-catalyzed [3 + 2] azide-acetylene coupling (CuAAC). The anti-colonization efficacy of the surfaces varied as a function of the antimicrobial activity of the peptides, and very effective surfaces could be prepared with a 6 log unit reduction in bacterial colonization.
Highlights
In the rich parts of the world, healthcare-associated infections (HAI) hit 1 of 14 hospitalized patients, often requiring additional treatment and extended hospitalization [1]
The pharmacophore predicts that all peptides prepared with at least two cationic charges and three bulky and lipophilic residues should have a minimum of antibacterial activity which is observed in the present library
In some of the peptides, the tryptophan residues were substituted with biphenylalanine, with a subsequent change in bulk, geometry, and lipophilicity that favors enhanced antibacterial efficacy [34,35], an effect observed in the present library, where the peptides in Series 2 were more effective than their Series 1 analogs
Summary
In the rich parts of the world, healthcare-associated infections (HAI) hit 1 of 14 hospitalized patients, often requiring additional treatment and extended hospitalization [1]. Indwelling medical devices (e.g., catheters) are prone to bacterial colonization on the surface and subsequent biofilm formation, leading to infections in the patient [6]. Biofilm-associated infections on indwelling medical devices prolong initial treatment regimens, increase antibiotic use, and add additional healthcare expenses for the hospital and society. Limited efficacy, unwanted toxicity, and the nondegradability of silver and other heavy metals have kept the medical device industry looking for better alternatives [12,14,15] Another issue with antibiotic-coated surfaces is the risk of contributing to the development of antibiotic resistance. Coating the surface with covalently attached antimicrobial peptides (AMPs) can be an alternative solution to the problem of medical device-associated infections [19,20]. Peptide 2d had potent activity against S. aureus (MIC: 4 μg/mL) and S. epidermidis (MIC: 2 μg/mL), but less activity against E. coli (MIC: 64 μg/mL) and was not active against P. aeruginosa (MIC: 256 μg/mL)
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