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Increasing resistance of  Pseudomonas aeruginosa  ( P. aeruginosa ) to conventional treatments demands the search for novel therapeutic strategies. In this study, the antimicrobial activity of dehydroleucodine (DhL), a sesquiterpene lactone obtained from  Artemisia (A.) douglasiana , was screened against several pathogenic virulence effectors of  P. aeruginosa .  In vitro , minimum inhibitory concentration of DhL was determined against  P. aeruginosa  strains PAO1, PA103, PA14, and multidrug resistant clinical strain, CDN118. Results showed that DhL was active against each strain where PAO1 and PA103 showed higher susceptibility (MIC 0.48 mg/mL) as compared to PA14 (MIC 0.96 mg/mL) and CDN118 (MIC 0.98 mg/mL). Also, when PAO1 strain was grown in the presence of DhL (MIC 50 , 0.12 mg/mL), a delay in the generation time was noticed along with significant inhibition of secretory protease and elastase activities, interruption in biofilm attachment phase in a stationary culture, and a significant decline in Type III effector ExoS. At MIC 50 , DhL treatment increased the sensitivity of  P. aeruginosa  towards potent antibiotics. Furthermore, treatment of  P. aeruginosa  with DhL prevented toxin-induced apoptosis in macrophages. These observations suggest that DhL activity was at the bacterial transcriptional level. Hence, antimicrobial activity of DhL may serve as leads in the development of new anti- Pseudomonas  pharmaceuticals.

A Novel Insight into Dehydroleucodine Mediated Attenuation ofPseudomonas aeruginosaVirulence Mechanism