Date of Award


Degree Type


Degree Name

Doctor of Philosophy (PhD)




Roy Welch

Subject Categories

Biology | Life Sciences | Microbiology


The complex life cycle of Myxococcus xanthus makes it a model organism for studying multicellular developmental processes in bacteria. In response to environmental changes, M. xanthus cells collectively and dramatically adjust their morphology, physiological functions, and biosynthesis. Particularly, M. xanthus copes with starvation by producing fruiting bodies filled with dormant and stress-resistant spores. During secondary metabolism, it synthesizes polyketide (PK) and non-ribosomal peptide (NRP) natural products that are crucial sources of antibiotics. Bacteria including M. xanthus, require the alternative σ54 regulatory system to initiate the transcription of necessary genes for settling stress and completing developmental process. This dissertation introduces in detail how σ54 system integrates regulatory events in transcription by applying σ54, targeted σ54 promoter DNA and corresponding activator proteins in mechanistic and genomic scales. Also, multicellular lifestyle of M. xanthus and natural products derived from myxobacteria are broadly reviewed.My first project has better defined the gene regulatory networks of M. xanthus in response to starvation, which are modulated by σ54 system and a transcriptional activator, Nla28. Specifically, highly conserved DNA sequence where Nla28 targets has been characterized; Direct Nla28-mediated developmental genes have been identified and verified; Regulatory pathways and biofunctions associated with M. xanthus starvation response have been profiled and classified. My second project investigated the hypothesis that 54 might be a common regulator of natural product genes in bacteria. The results suggest that M. xanthus employs σ54 system to regulate the transcription of at least some of its natural product genes after analyzing its potential natural product σ54 promoters. Also, it shows that these natural product gene regulations in M. xanthus are modulated by Nla28.


Open Access