Synergistic activity of sub-inhibitory concentrations of curcumin with ceftazidime and ciprofloxacin against Pseudomonas aeruginosa quorum sensing related genes and virulence traits

Abstract

Quorum sensing (QS) system in Pseudomonas aeruginosa may be an important target for pharmacological intervention. The present study aimed to investigate the synergetic activity of sub-MIC concentrations of curcumin (C) with ceftazidime (CAZ) and ciprofloxacin (CIP) against P. aeroginusa QS system. We determined the MIC and synergistic activity of C, CAZ and CIP against P. aeroginusa PAO1 using broth microdilution and checkerboard titration methods. The activity of sub-MIC (1/4 and 1/16 MIC) concentrations of C on the QS signal molecules was assessed using a reporter strain assay. The influence of sub-MIC of C, CAZ and CIP alone and in combination on motility and biofilm formation was also determined and confirmed by RT-PCR to test the expression of QS regulatory genes lasI, lasR, rhlI and rhlR. The addition of C decreased the MIC of CAZ and CIP. Curcumin showed synergistic effects with CAZ and additive activity with CIP. Treated PAO1 cultures in the presence of C showed significant reduction of signals C12-HSL and C4-HSL (P < 0.05). Sub-MIC concentrations (1/4 and 1/16 MIC) of C, CAZ and CIP alone and in combination significantly reduced swarming and twitching motilities and biofilm formation. Expression of QS regulatory genes lasI, lasR, rhlI, and rhlR using 1/4 MIC of C, CAZ and CIP alone and in combination was repressed significantly relative to untreated PAO1. Our results indicate that a combination of the sub-MIC concentration of C and CAZ exhibited synergism against P. aeroginusa QS system. This combination could lead to the development of a new combined therapy against P. aeruginosa.

Clinical Impact of Antibiotics for the Treatment of Pseudomonas aeruginosa Biofilm Infections

“…In a recent study, Otani et al (2018) showed that sub-MICs of ceftazidime reduce biofilm volume, inhibit twitching motility, and repress gene expression involved in bacterial adhesion and matrix production of P. aeruginosa PAO1. Roudashti et al (2017) had previously noticed this effect of cephalosporin on motility and biofilm formation for the same strain.…”

Activity of Cinnamaldehyde on Quorum Sensing and Biofilm Susceptibility to Antibiotics in Pseudomonas aeruginosa

“…The use of subinhibitory concentrations of macrolides was recently reported as another option for developing novel treatment strategies for P. aeruginosa infections [19]. Indeed, it has been shown that QS inhibitors work synergistically with antibiotics [20][21][22]. Thus, the application of QS inhibitors with standard antibiotics could be a promising strategy to attenuate biofilm infections [22,23].…”

Curcumin, an antibiotic resistance breaker against a multiresistant clinical isolate of Mycobacterium abscessus

“…Extensive research in the past half century has demonstrated that beside its antioxidant, anti‐inflammatory, and anticancer action, curcumin also exerts antimicrobial effects (Aggarwal et al, ). In particular, it has bactericidal activity, it can synergize with antibiotics, and it also targets the virulence factors of several pathogens (Brown, ; Packiavathy, Sasikumar, Pandian, & Veera, ; Roudashti, Zeighami, Mirshahabi, Bahari, Soltani, & Haghi ; Tyagi, Singh, Kumari, Kumari, & Mukhopadhyay, ). Nontuberculous, rapidly growing mycobacteria (RGM) belonging to the Mycobacterium abscessus complex ( M. abscessus subsp.…”