Site specific immobilization of a potent antimicrobial peptide onto silicone catheters: evaluation against urinary tract infection pathogens

Abstract

Bacterial colonization of urinary catheters is a common problem leading to Catheter Associated Urinary Tract Infections (CAUTIs) in patients, which result in high treatment costs and associated complications. Due to the advantages of antimicrobial peptides (AMPs) compared to most other antimicrobial molecules, an increasing number of AMP-coated surfaces is being developed but their efficacy is hindered by suboptimal coating methods and loss of peptide activity upon surface tethering. This study aims to address this issue by employing a methodic approach that combines a simple selective chemical immobilization platform developed on a silicone catheter with the choice of a potent AMP, Lasioglossin-III (Lasio-III), to allow site specific immobilization of Lasio-III at an effective surface concentration. The Lasio-III peptide was chemically modified at the N-terminal with a cysteine residue to facilitate cysteinedirected immobilization of the peptide onto a commercial silicone catheter surface via a combination of an allyl glycidyl ether (AGE) brush and polyethylene glycol (PEG) based chemical coupling. The amount of immobilized peptide was determined to be 6.59 AE 0.89 mg cm À2 by Sulfo-SDTB assay. The AMPcoated catheter showed good antimicrobial activity against both Gram positive and negative bacteria. The antimicrobial properties of the AMP-coated catheter were sustained for at least 4 days postincubation in a physiologically relevant environment and artificial urine and prevented the biofilm growth of E. coli and E. faecalis. Adenosine tri-phosphate leakage and propidium iodide fluorescence studies further confirmed the membranolytic mode of action of the immobilized peptide. To the best of our knowledge, this is the first proof-of-concept study that reports the efficacy of AMP immobilization by sulfhydryl coupling on a real catheter surface.

Design and surface immobilization of short anti-biofilm peptides

“…Coating of a 13mer GL13K peptide also made the titanium surface antibiofilm [49]. Likewise, immobilization of a 15mer lasioglossin LL-III to silicone catheters conferred antibiofilm ability to the device [50]. Recently, Xavier et al showed that synthetic lactams could also inhibit the growth of Streptococcus mutans on titanium [51].…”

A review of the recent advances in antimicrobial coatings for urinary catheters

“…However, some of the issues with AMPs are their suboptimal coating properties, potential toxicity, pH sensitivity and high cost of synthesis [10]. Some of these issues have been addressed recently, where Mishra et al immobilized peptides on silicone catheters [122]. A sulfhydryl coupling was used to immobilize the antimicrobial peptide, Lasio-III on the silicone urinary catheter.…”

Antifungal activity of cathelicidin peptides against planktonic and biofilm cultures of Candida species isolated from vaginal infections

“…Moreover, such sequences could be more suitable for chemical grafting onto materials of medical interest. It is worth to note that immobilized peptides often show a significantly reduced cytotoxic potential when compared to their soluble counterparts [33,47,63]. In this respect, ongoing studies are aimed at the identification of shorter peptide analogs and derivatives most suitable for chemical immobilization on biomedical materials.…”