Broad Host Range Peptide Nucleic Acids Prevent Gram-Negative Biofilms Implicated in Catheter-Associated Urinary Tract Infections

Abstract

Biofilms develop in sequential steps resulting in the formation of three-dimensional communities of microorganisms that are encased in self-produced extracellular polymeric substances. Biofilms play a key role in device-associated infections, such as catheter-associated urinary tract infections (CAUTIs), because they protect microorganisms from standard antimicrobial therapies. Current strategies to prevent biofilm formation in catheter-related infections, including prophylactic antibiotics and antibiotic-coated catheters, have been unsuccessful. This finding highlights a need for novel approaches to address this clinical problem. In this study, biofilm-forming phenotypes of common Gram-negative bacteria associated with CAUTIs were treated with antisense peptide nucleic acids (PNAs), and biofilm biomass and bacterial viability were quantified after 24 h of treatment. A cocktail of PNAs targeting the global regulator genes rsmA, amrZ, and rpoS in Pseudomonas aeruginosa significantly reduced viability and thus appropriately eliminated biofilm biomass. Antisense-PNAs against these same gene targets and the motility regulator gene motA inhibited biofilm formation among isolates of Klebsiella pneumoniae, Enterobacter cloacae, and Escherichia coli but did not reduce bacterial viability. These results suggest that antisense-PNAs are a promising new technology in preventing biofilm formation in urinary catheters, especially as a potential complement to conventional antimicrobials.