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

 

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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.

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