Electronic Theses and Dissertations

Date of Award

1-1-2021

Document Type

Dissertation

Degree Name

Ph.D. in Pharmaceutical Sciences

Department

Pharmaceutics and Drug Delivery

First Advisor

David C. Stevens

Second Advisor

Dale G. Nagle

Third Advisor

Sudeshna Roy

Relational Format

dissertation/thesis

Abstract

In the rhizosphere, plants curate and maintain distinct rhizobiome, some of which serve as secondary defense mechanisms against pathogenic microorganisms. Additionally, in response to biotic stress, plants generate phytohormones which regulate signaling pathways to activate systemic resistance. These phytohormones contribute to the chemical space within the rhizosphere in addition to other low-molecular-weight metabolites used for cell-to-cell communication within species and across kingdoms. However, little is known about the influences of stress-related phytohormones on beneficial bacteria even though biocontrol strategies abundantly explore plant-beneficial microorganisms to manage pathogens in agricultural systems. Myxobacteria are competent predators of plant pathogens and have demonstrated responses when exposed to exogenous quorum signals produced by prey bacteria. Our objective was to study the impacts of exogenous phytohormones and plant-related signals on myxobacterial motility, global transcriptome, and metabolism to reveal the potential roles of these bacteria in the rhizosphere. The plant-associated myxobacterium Archangium sp. strain Cb G35 exhibited a p < 0.05 increase in motility on exposure to methyljasmonate (MeJA), salicylic acid (SA), and abscisic acid (ABA) while transcriptomic studies revealed a ? fourfold change (p < 0.05) in the transcription for 56 genes in response to MeJA exposure. Untargeted analysis of LC-MS/MS datasets of crude extracts from exposure experiments with Global Natural Products Social Molecular Networking (GNPS) and XCMS-MRM tools further highlighted the activation and deactivation of specialized metabolites in response to these signals. Antibacterial assays of fractions from active extracts against E. coli revealed active metabolites of the terpene, fatty acid, and polyketide molecular families. However, before our investigations, only the bioactive roimantacene polyene, and p-hydroxyacetophenone amides have been associated with A. sp. While we have demonstrated the potential of observing signal-activated production of functional metabolites in the rhizosphere, our studies provide the condition-specific potential for discovering novel specialized metabolites that would contribute to natural product discovery.

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