Impact of long-term quorum sensing inhibition on uropathogenic <i>Escherichia coli</i>

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