Isolation and identification of natural product inhibitors of Plx2A, a toxin from Paenibacillus larvae

dc.contributor.advisorMerrill, Rod
dc.contributor.authorWood, Chantal of Molecular and Cellular Biologyen_US of Guelphen_US of Scienceen_US and Cellular Biologyen_US
dc.description.abstractMono-ADP-ribosyltransferase (mART) toxins are an important class of virulence factors generated by bacterial pathogens that promote many disease states in the target host. They catalyze the hydrolysis of the glycosidic bond joining nicotinamide with the N-ribose of NAD+ and transfer ADP-ribose to a target protein. Plx2A has recently been characterized as a mART toxin from the honey bee pathogen Paenibacillus larvae that plays a key role in American Foulbrood disease in honeybees. An HPLC-based NAD+-glycohydrolase assay was developed and used to reveal several plant extracts that demonstrated inhibition of Plx2A enzymatic activity. Additionally, a library of natural product-derived compounds chosen based on structure-guided modelling was tested against Plx2A, which identified one compound with inhibitory activity. The fractionation of the most promising extracts was achieved by solid-phase extraction with the analysis of these fractions by HPLC. Plant extracts provide novel lead inhibitors against these toxins to be used as potential therapeutics.en_US
dc.publisherUniversity of Guelphen_US
dc.rights.licenseAll items in the Atrium are protected by copyright with all rights reserved unless otherwise indicated.
dc.subjectPlant extractsen_US
dc.subjectmART toxinsen_US
dc.subjectAmerican Foulbrooden_US
dc.titleIsolation and identification of natural product inhibitors of Plx2A, a toxin from Paenibacillus larvaeen_US


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