Urinary tract infections (UTIs) are the most prevalent infectious diseases in community and clinical settings. The global emergence of multidrug-resistant (MDR) E. coli causing these UTIs necessitates exploring novel approaches. The use of compounds that attenuate bacterial virulence by acting through inhibition of quorum sensing (QS) is gathering momentum nowadays. This research was undertaken to investigate the anti-QS prospects of azithromycin (AZ) against 67 E. coli isolated from urine cultures of patients admitted to Alexandria Main University Hospital. Antibiotic susceptibility testing showed that 94% of these isolates were MDR. Swimming, twitching, and biofilm formation abilities were detected in 60%, 52.5%, and 55.2%, of the isolates, respectively. At its sub-inhibitory concentration, AZ hindered swimming and twitching motilities in 75% and 74.3% of the tested isolates, respectively. It reduced the biofilm formation by percentages ranging from 27% to 73%. Azithromycin downregulated the differential gene expression of luxS, a QS-regulating gene, and the genes encoding motility, thus proving its anti-QS ability. Further, the combinatory activity of AZ with ceftriaxone, ciprofloxacin, colistin, doxycycline, and tigecycline generated 95% of successful combinations.
In conclusion, AZ effectively attenuated the QS in urinary E. coli isolates, leading to a regression in the production of QS-associated virulence factors and hindrance of biofilm formation, thus delivering an avirulent pathogen. In addition, the synergistic combinations succeeded in circumventing the antibiotic resistance of E. coli isolates. Hence, AZ could be regarded as an anti-QS agent that might aid the design of innovative treatment alternatives for the management of UTIs caused by MDR E. coli.