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

CAPPER-PARKIN, K.L., NICHOL, T., SMITH, T.J., LACEY, M.M. and FORBES, S. (2023). Antimicrobial and cytotoxic synergism of biocides and quorum-sensing inhibitors against uropathogenic Escherichia coli. The Journal of hospital infection, 134, 138-146.

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Official URL: https://www.sciencedirect.com/science/article/pii/...
Open Access URL: https://www.sciencedirect.com/science/article/pii/... (Published version)
Link to published version:: https://doi.org/10.1016/j.jhin.2023.02.004
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    Abstract

    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 concentrations required to eradicate biofilms, limiting their antiseptic potential. Quorum-sensing inhibitors (QSIs) provide a novel anti-infective approach to disrupt biofilm formation on the catheter surface and help prevent CAUTIs.

    Aim

    To evaluate the combinatorial impact of biocides and QSIs at bacteriostatic, bactericidal 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, bactericidal, and biofilm eradication concentrations of test combinations in UPEC and combined cytotoxic effects in BSM cells.

    Findings

    Synergistic antimicrobial activity was observed between polyhexamethylene biguanide, benzalkonium chloride or silver nitrate in combination with either cinnamaldehyde or furanone-C30 against UPEC biofilms. However, furanone-C30 was cytotoxic at concentrations below those required for even 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.

    Item Type: Article
    Uncontrolled Keywords: Biocides; Catheter-associated urinary tract infections; Combinatorial therapies; Quorum-sensing inhibitors; Urinary tract infections; Uropathogenic Escherichia coli; 1103 Clinical Sciences; 1117 Public Health and Health Services; Epidemiology; 3202 Clinical sciences; 4202 Epidemiology; 4206 Public health
    Identification Number: https://doi.org/10.1016/j.jhin.2023.02.004
    Page Range: 138-146
    SWORD Depositor: Symplectic Elements
    Depositing User: Symplectic Elements
    Date Deposited: 06 Mar 2023 10:57
    Last Modified: 14 Mar 2023 13:30
    URI: https://shura.shu.ac.uk/id/eprint/31616

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