Development of Antimicrobial Impregnated Catheter Coatings to Prevent Uropathogenic Escherichia coli Infections

Abstract

Background: Urinary catheters are an essential medical device, used in the management of urinary incontinence and retention. However, catheters provide an abiotic surface upon which bacteria may colonise and form biofilms recalcitrant to immune clearance and antibiotic therapy. The incidence of catheter associated urinary tract infection (CAUTI) is a significant burden for healthcare systems, with uropathogenic Escherichia coli (UPEC) posing as one of the most common causative pathogens. The development of an effective anti-infective catheter coating which could prevent biofilm formation upon the catheter surface would be therefore have significant impact on improving the quality of life for catheterised patients. Methods: Presented here is a study into the development of potential antimicrobialcontaining sol-gel coatings to prevent UPEC colonisation and biofilm formation. Broad spectrum biocides and quorum sensing inhibitors (QSI) were evaluated for their potential as anti-infective coating agents both independently and in pairwise combinations to assess synergistic antimicrobial and cytotoxic activity. The impact of long-term biocide/QSI exposure on the bacterial transcriptome and proteome was determined and correlated to changes in bacterial susceptibility impacting overall coating efficacy. Biocides and QSIs were incorporated into a novel sol-gel coating system. Anti-biofilm potential was determined within a continuous culture drip flow reactor model and elution of antimicrobials from the sol-gel coating was determined via mass spectrometry. Results: Biocides and QSIs often displayed synergistic antibiofilm activity. The most promising initial combination of biocide and QSI was PHMB with cinnamaldehyde with regards to high antimicrobial activity and low cytotoxicity, however following incorporation into a sol-gel coating and evaluation in a drip flow model, silver nitrate with cinnamaldehyde demonstrated the best efficacy at reducing of biofilm formation. Long-term exposure to the test biocides and QSI led to a high number of changes within the transcriptome, frequently associated with regulation of motility associated genes, however this was not mirrored in the proteomics data, where fewer significantly differentially expressed proteins were observed. Regarding release of the test agents from the sol-gel coating, the elution of silver nitrate was rapid compared to the elution of BAC which did not elute readily from the coating. Conclusions: In the development of an antimicrobial impregnated catheter coating to prevent UPEC infection, the combination of silver nitrate with cinnamaldehyde demonstrates promise. The combination of silver nitrate with cinnamaldehyde was found to be synergistically antimicrobial, both antimicrobials elute from the coating, rapidly in the case of silver nitrate and slower in the case of cinnamaldehyde, and it was shown to reduce the biofilm formed within a continuous culture drip flow reactor model.