Abstract

The use of metal complexes to reduce or inhibit virulence factors of Pseudomonas aeruginosa is a promising strategy for the management and control of infections caused by this multidrug-resistant pathogen. The present study aimed to investigate the anti-quorum sensing activity of sub-minimum inhibitory concentrations (sub-MIC) of copper(II) sulfate pentahydrate-curcumin complex (Cu-CUR), iron(III) nitrate nonahydrate -curcumin complex (Fe-CUR), zinc(II) chloride-curcumin complex (Zn-CUR) and free curcumin (free-CUR) against P. aeruginosa PAO1. Metal-CUR complexes were synthesized and characterized by spectroscopic methods. The effect of sub-MIC (1/4 and 1/16 MIC) concentrations of metal-CUR complexes and free-CUR on cell growth, biofilm formation, motility, alginate and pyocyanin production, H2O2 susceptibility and expression of lasI and lasR genes in PAO1 was determined. MIC of metal-CUR complexes and free-CUR was determined as 62.5 and 125 µg/ml, respectively. Metal-CUR complexes at concentration of 62.5 µg/ml significantly reduced the cell growth to 1.5%–3.3%. Although we did not measure the anti-QS activity of metal-CUR complexes directly against PAO1, they indicated anti-QS activity in C. violaceum CV026. Copper-CUR complex at the concentration of 1/4 MIC showed the greatest inhibitory effect on swarming and twitching motilities, biofilm formation, alginate and pyocyanin production, sensitivity to H2O2 and reduction in the expression levels of lasI and lasR genes (P < 0.001). Considering the biological effects of Cu-CUR complex and its inhibitory activity on virulence factors, it may be used as an effective compound for treatment and control of infections caused by P. aeruginosa.

Highlights

  • Quorum sensing (QS) as a key two component bacterial system plays an important role in controlling of bacterial virulence factors

  • The present study aimed to investigate the antiquorum sensing activity of sub-minimum inhibitory concentrations (sub-minimum inhibitory concentration (MIC)) concentrations of copper(II) sulfate pentahydrate ­(CuSO4·5H2O)-curcumin complex (Cu-CUR), iron(III) nitrate nonahydrate (Fe(NO3)3·9H2O)-curcumin complex (Fe-CUR), zinc(II) chloride ­(ZnCl2)-curcumin complex (Zn-CUR) and free curcumin against P. aeruginosa PAO1

  • Copper-CUR complex at the concentrations of 1/4 MIC showed the greatest reduction in the Discussion Quorum sensing inhibitory activity of metal complexes is a promising strategy for treatment and control of bacterial infections (Behera et al 2012; Wang et al 2014; Ghosh et al 2015; Meza-Morales et al 2019b)

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Summary

Introduction

Quorum sensing (QS) as a key two component bacterial system plays an important role in controlling of bacterial virulence factors. Several investigations have reported the broad-spectrum anti-bacterial, anti-viral and anti-fungal activities of curcumin. It has antioxidant, anti-inflammatory and anti-cancer effects and has a potential against various diseases such as diabetes, allergies, arthritis, Alzheimer’s and other chronic diseases (Moghadamtousi et al 2014; Tyagi et al 2015). Previous studies have been carried out on the antibacterial activities of some metal-curcumin complexes but the effect of these compounds on P. aeruginosa QS system has not been demonstrated (Bagchi et al 2015; Syed et al 2015; Girish et al 2019; Tran Quang and Thao 2019). The present study aimed to investigate the antiquorum sensing activity of sub-MIC concentrations of copper(II) sulfate pentahydrate ­(CuSO4·5H2O)-curcumin complex (Cu-CUR), iron(III) nitrate nonahydrate (Fe(NO3)3·9H2O)-curcumin complex (Fe-CUR), zinc(II) chloride ­(ZnCl2)-curcumin complex (Zn-CUR) and free curcumin (free-CUR) against P. aeruginosa PAO1

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