Adjuvant effect of cranberry proanthocyanidin active fraction on antivirulent property of ciprofloxacin against Pseudomonas aeruginosa

• Combination of cranberry PAF and CIP were used as antivirulent agents against Pseudomonas aeruginosa.
• QS controlled virulence factors, motility and biofilms of P aeruginosa were significantly reduced on combination treatment.
• TLC profiles and docking analysis indicated that the agents act on different targets in QS network.

Quorum sensing inhibitors (QSIs) act as antivirulent agents since quorum sensing (QS) plays a vital role in regulating pathogenesis of Pseudomonas aeruginosa. However, application of single QSI may not be effective as pathogen is vulnerable to successful mutations. In such conditions, combination of QSIs can be exploited as there can be synergistic or adjuvant action. In the present study, we evaluated the antivirulence efficacy of combination of Vaccinium macrocarpon proanthocyanidin active fraction (PAF) and ciprofloxacin (CIP) at their sub-MICs using standard methods followed by analysis of their mode of action on QS using TLC and molecular docking. There was significant improvement in action of CIP when it was combined with PAF in reducing the QS controlled virulence factors (p < 0.05), motilities and biofilm of P. aeruginosa. TLC profiles of QS signals [(Acyl homoserine lactone (AHL) and Pseudomonas quinolone signal (PQS)] indicated that CIP in combination with PAF, besides showing inhibitory action on production of AHLs, also modulated production and inactivation of PQS. Docking scores also supported the observation. We therefore hypothesize that PAF-CIP combination, having improved anti-virulence property; can be exploited as a potent drug pairing against P. aeruginosa.

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