Impact of long-term quorum sensing inhibition on uropathogenic Escherichia coli.

HENLY, EL, NORRIS, K, RAWSON, K, ZOULIAS, N, JAQUES, L, CHIRILA, PG, PARKIN, KL, KADIRVEL, M, WHITEOAK, C, LACEY, Melissa, SMITH, TJ and FORBES, Sarah (2021). Impact of long-term quorum sensing inhibition on uropathogenic Escherichia coli. Journal of Antimicrobial Chemotherapy.

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Link to published version:: https://doi.org/10.1093/jac/dkaa517
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    Abstract

    BACKGROUND: Quorum sensing is an extracellular bacterial communication system used in the density-dependent regulation of gene expression and development of biofilms. Biofilm formation has been implicated in the establishment of catheter-associated urinary tract infections and therefore quorum sensing inhibitors (QSIs) have been suggested as anti-biofilm catheter coating agents. The long-term effects of QSIs in uropathogens is, however, not clearly understood. OBJECTIVES: We evaluated the effects of repeated exposure to the QSIs cinnamaldehyde, (Z)-4-bromo-5(bromomethylene)-2(5H)-furanone-C30 (furanone-C30) and 4-fluoro-5-hydroxypentane-2,3-dione (F-DPD) on antimicrobial susceptibility, biofilm formation and relative pathogenicity in eight uropathogenic Escherichia coli (UPEC) isolates. METHODS: MICs, MBCs and minimum biofilm eradication concentrations and antibiotic susceptibility were determined. Biofilm formation was quantified using crystal violet. Relative pathogenicity was assessed in a Galleria mellonella model. To correlate changes in phenotype to gene expression, transcriptomic profiles were created through RNA sequencing and variant analysis of genomes was performed in strain EC958. RESULTS: Cinnamaldehyde and furanone-C30 led to increases in susceptibility in planktonic and biofilm-associated UPEC. Relative pathogenicity increased after cinnamaldehyde exposure (4/8 isolates), decreased after furanone-C30 exposure (6/8 isolates) and varied after F-DPD exposure (one increased and one decreased). A total of 9/96 cases of putative antibiotic cross-resistance were generated. Exposure to cinnamaldehyde or F-DPD reduced expression of genes associated with locomotion, whilst cinnamaldehyde caused an increase in genes encoding fimbrial and afimbrial-like adhesins. Furanone-C30 caused a reduction in genes involved in cellular biosynthetic processes, likely though impaired ribonucleoprotein assembly. CONCLUSIONS: The multiple phenotypic adaptations induced during QSI exposure in UPEC should be considered when selecting an anti-infective catheter coating agent.

    Item Type: Article
    Uncontrolled Keywords: 0605 Microbiology; 1108 Medical Microbiology; 1115 Pharmacology and Pharmaceutical Sciences; Microbiology
    Identification Number: https://doi.org/10.1093/jac/dkaa517
    SWORD Depositor: Symplectic Elements
    Depositing User: Symplectic Elements
    Date Deposited: 26 Jan 2021 14:27
    Last Modified: 17 Mar 2021 14:30
    URI: http://shura.shu.ac.uk/id/eprint/28017

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