Antimicrobial and cytotoxic synergism of biocides and quorum-sensing inhibitors against uropathogenic Escherichia coli

Background: Uropathogenic Escherichia coli (UPEC) are a primary cause of catheter -associated urinary tract infections (CAUTIs), often forming mature recalcitrant biofilms on the catheter surface. Anti-infective catheter coatings containing single biocides have been developed but display limited antimicrobial activity due to the selection of biocide -resistant bacterial populations. Furthermore, biocides often display cytotoxicity at con-centrations required to eradicate biofilms, limiting their antiseptic potential. Quorum -sensing inhibitors (QSIs) provide a novel anti-infective approach to disrupt biofilm for-mation on the catheter surface and help prevent CAUTIs. Aim: To evaluate the combinatorial impact of biocides and QSIs at bacteriostatic, bac-tericidal and biofilm eradication concentrations in parallel to assessing cytotoxicity in a bladder smooth muscle (BSM) cell line. Methods: Checkerboard assays were performed to determine fractional inhibitory, bac-tericidal, and biofilm eradication concentrations of test combinations in UPEC and com-bined cytotoxic effects in BSM cells. Findings: Synergistic antimicrobial activity was observed between polyhexamethylene biguanide, benzalkonium chloride or silver nitrate in combination with either cinna-maldehyde or furanone-C30 against UPEC biofilms. However, furanone-C30 was cytotoxic at concentrations below those required even for bacteriostatic activity. A dose-dependent cytotoxicity profile was observed for cinnamaldehyde when in combination with BAC, PHMB or silver nitrate. Both PHMB and silver nitrate displayed combined bacteriostatic and bactericidal activity below the half-maximum inhibitory concentration (IC50). Triclosan in combination with both QSIs displayed antagonistic activity in both UPEC and BSM cells. Conclusion: PHMB and silver in combination with cinnamaldehyde display synergistic antimicrobial activity in UPEC at non-cytotoxic concentrations, suggesting potential as anti-infective catheter-coating agents.(c) 2023 The Author(s). Published by Elsevier Ltd on behalf of The Healthcare Infection Society. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).