Biocide exposure induces changes in susceptibility, pathogenicity and biofilm formation in Uropathogenic Escherichia coli

Background: Uropathogenic Escherichia coli (UPEC) are a frequent cause of catheter associated urinary tract infection (CAUTI). Biocides have been incorporated into catheter-coatings to inhibit bacterial colonisation whilst ideally exhibiting low cytotoxicity and mitigating the selection of resistant bacterial populations. We compared the effects of long-term biocide exposure on susceptibility, biofilm-formation and relative-pathogenicity in eight UPEC isolates.Methods: Minimum inhibitory concentrations (MIC), minimum bactericidal concentrations (MBC), minimum biofilm eradication concentrations (MBEC) and antibiotic susceptibilities were determined before and after long-term exposure to triclosan, polyhexamethylene biguanide (PHMB), benzalkonium chloride (BAC) and silver nitrate. Biofilm-formation was quantified using a crystal violet assay and relative-pathogenicity was assessed via a Galleria mellonella waxworm model. Cytotoxicity and resulting biocompatability index values were determined against an L929 murine fibroblast cell line.Results: Biocide exposure resulted in multiple decreases in biocide susceptibility in planktonic and biofilm associated UPEC. Triclosan exposure induced the largest frequency and magnitude of susceptibility decreases at MIC, MBC and MBEC, which correlated to an increase in biofilm biomass in all isolates. Induction of antibiotic-cross-resistance occurred in 6/84 possible combinations of bacteria, biocide and antibiotic. Relative-pathogenicity significantly decreased after triclosan exposure (5/8 isolates), increased after silver nitrate exposure (2/8 isolates) and varied between isolates for PHMB and BAC. Biocompatibility index ranked antiseptic potential as PHMB>triclosan>BAC>silver nitrate.Conclusion: Biocide exposure in UPEC may lead to reductions in biocide and antibiotic susceptibility, changes in biofilm-formation and alterations relative-pathogenicity. These data indicate the multiple consequences of biocide adaptation that should be considered when selecting an anti-infective catheter-coating agent.