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Impact of long-term quorum sensing inhibition on uropathogenic Escherichia coli. 2021

E L Henly, and K Norris, and K Rawson, and N Zoulias, and L Jaques, and P G Chirila, and K L Parkin, and M Kadirvel, and C Whiteoak, and M M Lacey, and T J Smith, and S Forbes
Biomolecular Sciences Research Centre, Sheffield Hallam University, Sheffield, UK.

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. 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. 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. 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. The multiple phenotypic adaptations induced during QSI exposure in UPEC should be considered when selecting an anti-infective catheter coating agent.

UI MeSH Term Description Entries
D008826 Microbial Sensitivity Tests Any tests that demonstrate the relative efficacy of different chemotherapeutic agents against specific microorganisms (i.e., bacteria, fungi, viruses). Bacterial Sensitivity Tests,Drug Sensitivity Assay, Microbial,Minimum Inhibitory Concentration,Antibacterial Susceptibility Breakpoint Determination,Antibiogram,Antimicrobial Susceptibility Breakpoint Determination,Bacterial Sensitivity Test,Breakpoint Determination, Antibacterial Susceptibility,Breakpoint Determination, Antimicrobial Susceptibility,Fungal Drug Sensitivity Tests,Fungus Drug Sensitivity Tests,Sensitivity Test, Bacterial,Sensitivity Tests, Bacterial,Test, Bacterial Sensitivity,Tests, Bacterial Sensitivity,Viral Drug Sensitivity Tests,Virus Drug Sensitivity Tests,Antibiograms,Concentration, Minimum Inhibitory,Concentrations, Minimum Inhibitory,Inhibitory Concentration, Minimum,Inhibitory Concentrations, Minimum,Microbial Sensitivity Test,Minimum Inhibitory Concentrations,Sensitivity Test, Microbial,Sensitivity Tests, Microbial,Test, Microbial Sensitivity,Tests, Microbial Sensitivity
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000900 Anti-Bacterial Agents Substances that inhibit the growth or reproduction of BACTERIA. Anti-Bacterial Agent,Anti-Bacterial Compound,Anti-Mycobacterial Agent,Antibacterial Agent,Antibiotics,Antimycobacterial Agent,Bacteriocidal Agent,Bacteriocide,Anti-Bacterial Compounds,Anti-Mycobacterial Agents,Antibacterial Agents,Antibiotic,Antimycobacterial Agents,Bacteriocidal Agents,Bacteriocides,Agent, Anti-Bacterial,Agent, Anti-Mycobacterial,Agent, Antibacterial,Agent, Antimycobacterial,Agent, Bacteriocidal,Agents, Anti-Bacterial,Agents, Anti-Mycobacterial,Agents, Antibacterial,Agents, Antimycobacterial,Agents, Bacteriocidal,Anti Bacterial Agent,Anti Bacterial Agents,Anti Bacterial Compound,Anti Bacterial Compounds,Anti Mycobacterial Agent,Anti Mycobacterial Agents,Compound, Anti-Bacterial,Compounds, Anti-Bacterial
D014552 Urinary Tract Infections Inflammatory responses of the epithelium of the URINARY TRACT to microbial invasions. They are often bacterial infections with associated BACTERIURIA and PYURIA. Infection, Urinary Tract,Infections, Urinary Tract,Tract Infection, Urinary,Tract Infections, Urinary,Urinary Tract Infection
D053038 Quorum Sensing A phenomenon where microorganisms communicate and coordinate their behavior by the accumulation of signaling molecules. A reaction occurs when a substance accumulates to a sufficient concentration. This is most commonly seen in bacteria. Quorum Quenching,Quenching, Quorum,Quenchings, Quorum,Quorum Quenchings,Sensing, Quorum
D056689 Uropathogenic Escherichia coli Strains of Escherichia coli that preferentially grow and persist within the urinary tract. They exhibit certain virulence factors and infection pathways that cause URINARY TRACT INFECTIONS. Uropathogenic E. coli
D018441 Biofilms Encrustations formed from microbes (bacteria, algae, fungi, plankton, or protozoa) embedded in an EXTRACELLULAR POLYMERIC SUBSTANCE MATRIX that is secreted by the microbes. They occur on body surfaces such as teeth (DENTAL DEPOSITS); inanimate objects, and bodies of water. Biofilms are prevented from forming by treating surfaces with DENTIFRICES; DISINFECTANTS; ANTI-INFECTIVE AGENTS; and anti-fouling agents. Biofilm

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