Selective isolation of Burkholderia, untargeted metabolomics, and biofilm inhibition screening for the discovery of bacterial natural products

Date created: 
Natural products
Mass spectrometry
High-throughput image-based screening

The study of natural products is dedicated to the discovery, evaluation, and use of specialized metabolites from natural sources for crop, animal, and human health. The methods required to isolate, characterize, and find utility for these important compounds are continually developing and finding new methods for exploring the diversity of chemistry available in the natural world. This work explores methods in selecting source organisms, comparison of the resulting natural products extracts with an established source of bioactive compounds, and biological screening of a vast library for the discovery of compounds for potential medical use. In the course of this work, a new and robust selection method is described for the one-step isolation of Burkholderia from complex environmental samples. This method introduces a systematic methodology for isolation of other priority organisms. The comparative untargeted metabolomics of the extracts from the Burkholderia library with an existing library of marine actinobacteria highlights the value of continued exploration of both new taxa and additional strains of known organisms for the discovery of important natural products. Finally, the high-throughput image-based screening of extracts and pure compounds for the inhibition and dispersion of V. cholerae biofilms highlights the difficulty and utility of natural products drug discovery for potential medical applications. This work demonstrates the various and important facets of natural products research from the beginning acquisition of organisms and their resulting compounds to the evaluation of these molecules prior to clinical use.

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This thesis may be printed or downloaded for non-commercial research and scholarly purposes. Copyright remains with the author.
Roger G. Linington
Science: Department of Chemistry
Thesis type: 
(Thesis) Ph.D.