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Breaking bad: Better call gingerol for improving antibiotic susceptibility of Pseudomonas aeruginosa by inhibiting
Arpit Shukla1, Paritosh Parmar2, Baldev Patel2
1Department of Microbiology & Biotechnology, University School of Sciences, Gujarat University, Ahmedabad, 380009, Gujarat, India; Department of Biological Sciences & Biotechnology, Institute of Advanced Research, Gandhinagar, 382426, Gujarat, India.
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.
Insights
Gingerol inhibits quorum sensing (QS) pathways in Pseudomonas aeruginosa, a multi-antibiotic resistant
Area of Science:
- Microbiology
- Bacteriology
- Drug Discovery
Background:
- Pseudomonas aeruginosa is a multidrug-resistant 'superbug' causing significant infections.
- Bacterial pathogenicity is often regulated by quorum sensing (QS), a cell-cell communication system.
- QS pathways are crucial for P. aeruginosa virulence and pose challenges for antibiotic treatment.
Purpose of the Study:
- To investigate gingerol as a potential quorum sensing inhibitor (QSI) against P. aeruginosa.
- To evaluate gingerol's efficacy in disrupting QS-mediated virulence factors.
- To assess the combined effect of gingerol and antibiotics against P. aeruginosa.
Main Methods:
- In silico analysis to predict gingerol's interaction with QS receptors (LasR, PhzR, RhlR).
- In vitro validation of gingerol's impact on EPS, biofilm, pyocyanin, and rhamnolipid production.
- Assessment of gingerol's synergistic effect with ciprofloxacin on bacterial growth.
Main Results:
- Gingerol effectively interfered with key QS receptors in P. aeruginosa.
- Gingerol significantly reduced virulence factors including EPS, biofilm, pyocyanin, and rhamnolipid.
- Gingerol enhanced the antibacterial activity of ciprofloxacin, demonstrating synergistic effects.
Conclusions:
- Gingerol shows promise as a novel quorum sensing inhibitor against P. aeruginosa.
- Combining QSIs like gingerol with conventional antibiotics offers a potent strategy against antibiotic resistance.
- This integrated approach could provide a holistic solution for combating multidrug-resistant bacterial infections.
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