Date of Award
12-1-2025
Document Type
Dissertation
Degree Name
Ph.D. in Pharmaceutical Sciences
First Advisor
Cole Stevens
Second Advisor
Paul Boudreau
Third Advisor
Marc Slattery
School
University of Mississippi
Relational Format
dissertation/thesis
Abstract
Myxobacteria are prolific producers of specialized metabolites and key contributors to microbial interactions within soil and other environments, yet fundamental questions remain about the conservation of their biosynthetic capacities and the dynamics that shape their coexistence with neighboring microorganisms. This dissertation addresses these gaps through three integrated research directions. In Chapter 2 we utilized a pan-genome framework across eleven genera and 195 sequenced genomes,including ten newly reported isolates, and found five BGCs were identified as the conserved BGCs across the Myxococcota. These clusters encode metabolites with established ecological functions, none of which are known toxins, suggesting selective maintenance of signaling and stress-response pathways in myxobacteria. Conservation patterns were further validated in genera with limited genomic representatives, supporting genus-level trends in specialized metabolism. Notably, the indigoidine BGC, typically associated with Streptomyces, was consistently conserved in Melittangium. Heterologous expression of the core biosynthetic gene (bspA) in Escherichia coli and subsequent detection of indigoidine verified the identity and functionality of this pathway, highlighting the evolutionary persistence of key metabolic features across the phylum. Chapter 3 focuses on characterizing newly isolated swarm communities with myxobacteria and a companion bacteria Microvirga that resist cultivation as monoculture. Based on reisolation and repeated cultivation, we were able to say that the swarm consortia are stable and amenable to laboratory conditions and not just a serendipitously isolated bacteria with similar cultivation preferences. Furthermore, metagenomic analysis, comparative genomics and genome scale metabolic modeling of the consortia shows there is an association between myxobacteria, and Microvirga spp. indicating potential for intra-bacterial symbiosis in swarm communities and Chapter 4 focuses on investigating the metatranscriptional foundations for understanding the functional roles of individual members within the consortia over time. Differential gene expression in early stationary phase of growth shows upregulation of genes involved in AHL synthases from both members of the consortia while in late stationary phase there is upregulation of genes involved in quorum quencing (AHL hydrolases) from myxobacteria in the consortia. The presence of this quorum sensing features in consortia indicate inter-bacterial signaling.
Recommended Citation
Khanal Pokharel, Shailaja, "Uncovering Conserved Biosynthetic Gene Clusters and Interbacterial Interactions of Myxobacteria in Polymicrobial Communities" (2025). Electronic Theses and Dissertations. 3520.
https://egrove.olemiss.edu/etd/3520