Breaking bad: Better call gingerol for improving antibiotic susceptibility of Pseudomonas aeruginosa by inhibiting multiple quorum sensing pathways

Abstract

Pseudomonas aeruginosa is recognized as a bacterium with many bullets in its armoury and the Achilles heel of the bacterium is that it exudes several pathways that lead to pathogenicity thereby making the application of the strain cautious since the bacterium is known as a ‘superbug’ ergo, being resistant to multiple antibiotics. The mechanisms of pathogenicity are mainly driven by quorum sensing (QS), a phenomenon that works on cell-cell communication through classical ligand-receptor interactions. QS-mediated pathways enable control of this organism impossible even with the use of antibiotics. Henceforth, interfering with the QS pathways serves as a new mode of action for futuristic antibiotics to decrease the distress of this microbe. We propose gingerol to interfere with various QS-receptors of P. aeruginosa (LasR, PhzR and RhlR) which were deduced using in silico approach and validated in vitro by assessing its impact on EPS, biofilm, pyocyanin and rhamnolipid of the microbe. Further, gingerol was found to increase the antibacterial potency of the antibiotic when applied in integration with ciprofloxacin. The findings provide an insight about preferring the integrated approach of using QS-inhibitors (QSI) in tandem with antibiotics for holistic strategy in fight against the phenomenon of antibiotic resistance acquired by microbes.