title: 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 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 (MIC50, 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 MIC50, 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.
authors.affiliation: Department of Biological Sciences, Florida International University, Miami, FL 33199, USA.
authors.forename: S
authors.initials: S
authors.lastname: Mustafi
authors.affiliation: Biomolecular Sciences Institute, Florida International University, Miami, FL 33199, USA.
authors.forename: M L
authors.initials: ML
authors.lastname: Veisaga
authors.affiliation: Laboratory of Cytoskeleton and Cell Cycle, Institute of Histology and Embryology, Faculty of Medicine, National University of Cuyo, 5500 Mendoza, Argentina.
authors.forename: L A
authors.initials: LA
authors.lastname: López
authors.affiliation: Department of Biological Sciences, Florida International University, Miami, FL 33199, USA ; Biomolecular Sciences Institute, Florida International University, Miami, FL 33199, USA ; Fairchild Tropical Botanic Garden, 10901 Old Cutler Road, Coral Gables, FL 33156, USA ; International Center of Tropical Botany, Florida International University, Miami, FL 33199, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Barbieri
mesh_terms: D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D019306:Artemisia / Q000737:chemistry; D018441:Biofilms / Q000187:drug effects*; D006801:Humans; D007783:Lactones / Q000008:administration & dosage* / Q000737:chemistry; D008826:Microbial Sensitivity Tests; D011552:Pseudomonas Infections / Q000188:drug therapy* / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000472:pathogenicity; D012717:Sesquiterpenes / Q000008:administration & dosage* / Q000737:chemistry
chemical_list: D000900:Anti-Bacterial Agents; D007783:Lactones; D012717:Sesquiterpenes; C079949:dehydroleucodine