Degree

Doctor of Philosophy (PhD)

Department

biological sciences

Document Type

Dissertation

Abstract

Burkholderia thailandensis shares strong genomic similarity with highly pathogenic members of the genus and serves as a surrogate for studies of pathogenic Burkholderia biology. As growth conditions become limiting, B. thailandensis transitions into stationary phase, and it encounters fluctuating pH across environmental habitats and within host-associated niches. Understanding the molecular mechanisms that characterize growth-state transitions and responses to physiologically relevant pH changes is therefore critical for understanding bacterial adaptation to stress.

First, I present integrated transcriptomic and proteomic analyses of mRNA expression and protein abundance changes during entry into the stationary phase. During this transition, I identified 928 differentially expressed mRNAs and 832 differentially accumulating proteins. These changes reflected coordinated metabolic and regulatory reprogramming. Only a modest positive correlation between transcriptome and proteome changes was observed. Although RpoS is widely recognized as a central regulator of stationary-phase adaptation in Gram-negative bacteria, its abundance did not significantly increase, indicating that regulatory mechanisms independent of changes in RpoS abundance may contribute to the observed adaptation.

Next, I examined responses to acute exposure to an external pH of 6.0 and pH 8.0 compared to pH 7.0, using quantitative mass spectrometry–based proteomics with complementary transcriptome profiling for pH 8.0. At pH 6.0, four proteins were depleted and four accumulated, whereas at pH 8.0, 13 proteins accumulated and 14 were depleted. Exposure to both pH 6.0 and pH 8.0 resulted in depletion of OpcP-family outer membrane porins and reduction of ribosomal, flagellar, and beta-lactam resistance pathways. Consistent with these changes, phenotypic assays indicated modified beta-lactam resistance and a marked reduction in surface motility at pH 6.0 and 8.0 compared to pH 7.0. At pH 8.0, genes related to chemotaxis and flagellar motility were downregulated, while genes encoding bactobolin biosynthesis were upregulated. Bactobolins are polyketide–peptide antibiotics that inhibit translation and their induction at pH 8.0 suggests that mildly alkaline conditions may trigger secondary metabolite production as part of an adaptive competitive strategy.

Taken together, these findings define how environmental stressors impact bacterial adaptive mechanisms and potentially guide strategies to predict or mitigate antimicrobial resistance.

Date

4-17-2026

Committee Chair

Anne Grove

LSU Acknowledgement

1

LSU Accessibility Acknowledgment

1

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