Inhibition of Pseudomonas aeruginosa quorum sensing by subinhibitory concentrations of metal-ciprofloxacin complexes

Introduction and Objectives: Pseudomonas aeruginosa quorum sensing (QS) system is a cell to cell signaling mechanism that regulates virulence factors and pathogenicity. Therefore, the QS system in P. aeruginosa may be an important target for pharmacological intervention. The present study aimed to investigate the effects of sub-minimum inhibitory concentrations (sub-MIC) of metal-ciprofloxacin complexes against P. aeruginosa quorum sensing related virulence factors. Materials and Methods: After synthesis and structural confirmation of metal- ciprofloxacin complexes (cu-cip, zn-cip, mn-cip and co-cip) using NMR, FTIR and X-ray, the MIC of ciprofloxacin alone and metal complexes was detected against P. aeruginosa PAO1 using broth microdilution method. The effect sub-MIC (1/4 and 1/16 MIC) concentrations of these compounds on motility and biofilm formation was also determined. Results: MIC of ciprofloxacin and metal-ciprofloxacin complexes was 0.125 μg/ml. A significant decrease (ranged from 15% to 53.6%) in biofilm formation was observed when PAO1 strain was grown with 1/4 and 1/16 MIC of all compounds (P< 0.05). The inhibitory effect was concentration dependent. The concentration of 1/4 of co-ciprofloxacin demonstrated greater inhibition of biofilm formation with 53.6%. Furthermore, these components with 1/4 and 1/16 of MIC reduced swarming and twitching motilities ranged from 15-57%. Conclusion: The results indicate that sub-MIC of metal-ciprofloxacin complexes exhibited inhibitory effects against P. aeroginusa QS related virulence factors. These compounds could lead to the development of alternative therapeutics against P. aeruginosa.

کلیدواژه ها:

Metal –ciprofloxacin complexes ، Pseudomonas aeruginosa ، Quorum sensing.