A novel insight into Dehydroleucodine mediated attenuation of Pseudomonas aeruginosa virulence mechanism

Abstract

Increasing resistance of Pseudomonas aeruginosa (P. aeruginosa) to conventional treatments demands the search for noveltherapeutic strategies. In this study, the antimicrobial activity of dehydroleucodine (DhL), a sesquiterpene lactone obtainedfrom Artemisia (A.) douglasiana, was screened against several pathogenic virulence effectors of P. aeruginosa. In vitro, minimuminhibitory concentration of DhL was determined against P. aeruginosa strains PAO1, PA103, PA14, and multidrug resistant clinicalstrain, CDN118. Results showed that DhL was active against each strain where PAO1 and PA103 showed higher susceptibility (MIC0.48 mg/mL) as compared to PA14 (MIC 0.96 mg/mL) and CDN118 (MIC 0.98 mg/mL). Also, when PAO1 strain was grown inthe presence of DhL (MIC50, 0.12 mg/mL), a delay in the generation time was noticed along with significant inhibition of secretoryprotease and elastase activities, interruption in biofilm attachment phase in a stationary culture, and a significant decline in Type IIIeffector ExoS. At MIC50, DhL treatment increased the sensitivity of P. aeruginosa towards potent antibiotics. Furthermore, treatmentof P. aeruginosa with DhL prevented toxin-induced apoptosis in macrophages. These observations suggest that DhL activity wasat the bacterial transcriptional level. Hence, antimicrobial activity of DhL may serve as leads in the development of new antiPseudomonaspharmaceuticals.