Characterizing The Transcriptional Regulation Of The Dlp12 Lysis Cassette And Its Effects On Curli Expression And Biofilm Formation In Escherichia Coli.
Bacteria often exist in elaborate communities known as biofilms. These biofilms are inherently resistant to environmental insults such as osmotic stress, desiccation, antibiotic treatment, and immune system attack. As such, bacteria in biofilms are regularly the cause of nosocomial infections and represent a significant threat to human health. The resilient nature of biofilm structures has prompted significant research in the regulatory pathways that govern biofilm formation and maintenance. By acquiring comprehensive knowledge of biofilm forming signaling pathways, we could elucidate novel drug targets to either disperse existing biofilms or prevent their formation altogether. Here, we describe how YbcQ and RpoE affect the regulation of the genes encoding a defective lambdoid prophage's (DLP12) lysis machinery and demonstrate how loss of YbcQ impacts curli production in E. coli. By demonstrating that mutants defective in peptidoglycan recycling can rescue the curli deficient phenotype of ybcQ mutants we provide preliminary evidence for a mechanistic link between peptidoglycan recycling and curli expression and biofilm formation. Our work ends with the discovery that the peptidoglycan degradation product GlcNAc-6P appears to serves as a previously unappreciated global effector by derepressing NagC regulation of H-NS expression. We therefore propose that NagC is as actually an important global super-regulator in E. coli, sensing changes in peptidoglycan status by responding to changes in GlcNAc-6P and subsequently modulating a significant subset of cellular regulatory pathways via H-NS. This work furthers our understanding of fundamental processes regulating biofilm formation and lays the foundation for understanding how a previously unappreciated signal of cell wall status is sensed by the bacteria, and how that signal is involved in regulating the production of proteins that are important for adherence to surfaces and the ability to form biofilms. This pathway could prove a potential target for combating biofilm communities associated with chronic infection or biofouling in engineered systems.
Hay, Anthony G.
Peters, Joseph E.; Roberts, Jeffrey Warren
Ph.D. of Microbiology
Doctor of Philosophy
dissertation or thesis