Chinese medicinal herb extract inhibits PQS-mediated quorum sensing system in Pseudomonas aeruginosa.

Abstract

Chinese medicinal herbs have long been recognized as important resources that can be used for the struggle against diseases and a significant component of health care system for thousands of years. In order to understand their roles in the treatment against bacterial infections, we examined the underlying mechanisms of one of the medicinal herb extracts (MHE) (Artemisiae argyi Folium, the root bark of Cortex dictamni and the root of Solanum melongena) on the human opportunistic pathogen Pseudomonas aeruginosa. We combined phenotypic assays, transcriptional analysis and chemical investigations to identify the mechanisms underlying MHE inhibition. The standard sample was prepared and transcriptional reporters for quorum sensing systems were constructed. Electrophoretic mobility shift assays were used to clarify the mechanism. GC-MS and molecular docking were used to identify the chemicals in MHE and potential binding agents. We found that co-culturing of MHE with bacterial cells did not change the growth rate but substantially attenuate the production of virulence factors such as phenazine pyocyanin, siderophore pyoverdine and biofilm formation. Transcriptional responses of three major quorum sensing (QS) systems of P. aeruginosa to MHE showed that Pseudomonas quinolone signaling (PQS) system was completely repressed, rhlR/rhlI QS system was moderately inhibited, while lasR/lasI QS system was only slightly affected, suggesting that MHE might selectively target the PQS system to inhibit bacterial virulence. Furthermore, electrophoretic mobility shift assays (EMSA) showed that MHE inhibited the binding of MvfR the corresponding pqsA promoter region, suggesting that MHE serves as a competitive agent to quench the QS functionality in P. aeruginosa. We prove that MHE functions as an effective countermeasure against bacterial infections.