Innovative application of ceftriaxone as a quorum sensing inhibitor in Pseudomonas aeruginosa

Pseudomonas aeruginosa is a Gram-negative bacterium that has the potential to induce various healthcare-related infections through its array of virulence factors. The control of virulence factor expression is mainly regulated by a communication process among cells called quorum sensing (QS). Blocking QS could be a viable tactic to suppress virulence factors and reduce pathogenicity without impacting bacterial growth. This approach has the potential to significantly decrease the multiple drug resistance emergence. In this study, we explored the impact of ceftriaxone (CRO), which is a commonly used beta-lactam antibiotic, and its metal derivatives on the QS system and virulence factors of both standard strains and clinical isolates of P. aeruginosa. The quorum sensing inhibitory (QSI) activity of CRO and ceftriaxone Nickel complex (CRON) was evaluated. The minimum inhibitory concentration (MIC) was determined and the effect of sub-MICs of CRO and CRON was assessed on P. aeruginosa strains virulence factors. CRO and CRON effectively suppressed the virulence factors of P. aeruginosa strains at sub-MICs, without altering bacterial viability. Additionally, a molecular docking investigation was carried out to identify potential mechanisms of QSI. CRO and CRON exhibited high ICM scores, potentially displacing natural ligands when interacting with LasR, LasI, and PqsR receptors.