Nonsteroidal Anti-inflammatory Drugs Reduce the Production of Quorum Sensing Regulated Virulence Factors and Swarming Motility in Human Pathogen Pseudomonas aeruginosa

Abstract

Antibiotics are commonly used for the treatment of microbial infections. With the widespread appearance of multi antibiotic-resistant bacteria, it is becoming increasingly more difficult to treat bacterial infections with conventional antibiotics. Thus, there is an increasing need for new strategies to cope with infectious diseases. The discovery that many pathogenic bacteria employ quorum sensing (QS) to regulate their pathogenicity and virulence factor production makes the QS system an attractive target for antimicrobial therapy. It has been suggested that inactivating the QS system of a pathogen can result in a significant decrease in virulence factor production. In this study, a variety of NSAIDs, such as diclofenac, ibufen, ketoprofen, naproxen, piroxicam were screened for their capacity to reduce the production of QS-regulated virulence factors and swarming motility in the human pathogen P. aeruginosa. Ketoprofen, diclofenac, ibufen, naproxen and piroxicam reduced the elastase production by 28-47% compared to the untreated cultures. Pyocyanin production was also inhibited by these compounds but to a lesser extent. In swarming assay plates, ketoprofen and diclofenac treated PA01 strain displayed significant reductions in swarming motility (81% and 84% respectively). These findings suggest that especially, ketoprofen and diclofenac, may prevent bacterial colonization, and thereby reducing biofilm formation, by interfering with QS-controlled swarming motility of P. aeruginosa and combinatory chemotherapy with both conventional antibiotics and tested NSAIDs could be used for the treatment of chronic infections caused by P. aeruginosa and other clinically important pathogens which regulate their pathogenicity via QS.

Meloxicam inhibits biofilm formation and enhances antimicrobial agents efficacy by Pseudomonas aeruginosa

“…It is considered that this kind of effect should be due to inhibition of bacterial initial attachment (Demirag, Esen, Zivalioglu, Leblebicioglu, & Keceligil, ; Muller, Al‐Attar, Wolff, & Farber, ), reduction of EPS and protein syntheses (Farber & Wolff, ; Muller et al., ), and change of hydrophobicity (Naves et al., ). Another possible interpretation for biofilm inhibition is their impact on the QS system (Ulusoy & Bosgelmez‐Tinaz, ). QS system is a bacterial communication process that depends on the bacterial population density.…”

Inhibitors of Bacterial Swarming Behavior

“…The anti‐inflammatory drugs diclofenac and also ketoprofen were shown to inhibit swarming motility of P. aeruginosa at 5 m m concentration without any growth inhibition. Reduced production of virulence factors as well as activity in an AHL‐quorum‐sensing inhibition screen suggested that these compounds inhibited swarming through the quorum‐sensing circuits with the molecular targets yet to be identified . A diazaborine‐based copolymer with quorum‐sensing inhibitory activity in a violacein assay showed swarming inhibition by about 50 % against P. aeruginosa PAO1 at a concentration of 100 μg mL −1 , whereas the MIC (minimal inhibitory concentration) was determined to be 10 times higher .…”

Identification of the Hypertension Drug Guanfacine as an Antivirulence Agent in Pseudomonas aeruginosa

“…By contrast, several β‐lactams, such as piperacillin ( 4 ) and cephalosporin antibiotics (see below) appeared to further enhance the expression of virulence factors. Because of the previously established roles of anti‐inflammatory agents as potential quorum quenchers in P. aeruginosa , we focused on the effects of cephalosporins and guanfacine. We have herein not addressed the effects of anti‐Parkinson's drugs further, but this topic certainly deserves further attention.…”