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 <i>rsmA</i>, <i>amrZ</i>, and <i>rpoS</i> in <i>Pseudomonas aeruginosa</i> significantly reduced viability and thus appropriately eliminated biofilm biomass. Antisense-PNAs against these same gene targets and the motility regulator gene <i>motA</i> inhibited biofilm formation among isolates of <i>Klebsiella pneumoniae</i>, <i>Enterobacter cloacae</i>, and <i>Escherichia coli</i> 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.