Microbial pathogenesis
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Microbial pathogenesis · May 2018
Attenuation of quorum sensing regulated virulence and biofilm development in Pseudomonas aeruginosa PAO1 by Diaporthe phaseolorum SSP12.
In recent years, Pseudomonas aeruginosa PAO1 emerged as the significant pathogenic microorganism in majority of the hospital-acquired infections due to its resistance to the conventional antibiotics by virtue of its highly organized quorum sensing and associated biofilm formation. In the present study, quorum sensing attenuation potential of Diaporthe phaseolorum SSP12 extract was investigated against P. aeruginosa PAO1 amply supported by molecular docking studies. D. phaseolorum SSP12 extract significantly inhibited the production of LasI/R mediated LasA protease, LasB elastase and chitinase with 66.52 ± 5.41, 71.26 ± 4.58 and 61.16 ± 4.28% of inhibition respectively at a concentration of 750 μg mL-1. ⋯ The presence of bioactive constituents such as phenyl ethylalcohol, 2, 4-di-tert-butylphenol, fenaclon, 1, 4-phenylenediacetic acid, and benzyl hydrazine in D. phaseolorum SSP12 extract was evident from Gas chromatography-mass spectrophotometric (GC-MS) analysis. From the in silico molecular docking studies, fenaclon and 2, 4-di-tert-butylphenol competitively binds to QS receptors LasR and RhlR and alters the binding of its cognate ligands and modulates the expression of virulence phenotypes. The promising anti quorum sensing efficacy of D. phaseolorum SSP12 extract suggested new avenues for development of anti-infective drugs from fungal derived metabolites to counteract the problems associated with conventional antibiotic therapies.
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Microbial pathogenesis · May 2018
Attenuation of quorum sensing controlled virulence factors and biofilm formation in Pseudomonas aeruginosa by pentacyclic triterpenes, betulin and betulinic acid.
The production of virulence determinants and biofilm formation in numerous pathogens is regulated by the cell-density-dependent phenomenon, Quorum sensing (QS). The QS system in multidrug resistant opportunistic pathogen, P. aeruginosa constitutes of three main regulatory circuits namely Las, Rhl, and Pqs which are closely linked to its pathogenicity and establishment of chronic infections. In spite intensive antibiotic therapy, P. aeruginosa continue to be an important cause of nosocomial infections and also the major cause of mortality in Cystic Fibrosis patients with 80% of the adults suffering from chronic P. aeruginosa infection. ⋯ Based on the in vivo studies, the test compounds notably enhanced the survival of Caenorhabditis elegans infected with P. aeruginosa. Furthermore, molecular docking analysis revealed that BT and BA can act as a strong competitive inhibitor for QS receptors, LasR and RhlR. The findings suggest that BT and BA can serve as potential anti-infectives in the controlling chronic infection of P. aeruginosa.