Metabolic control is key for the survival of every organism. Despite years of studies, newly identified genes have been discovered in bacteria that play a great role in controlling metabolism. Additionally, new data suggests that even for Escherichia coli, there is strain-to- strain variation in their preferred nutrient sources. Much of this variation appears linked to the niche the strain inhabits, whether it is the intestine, urinar tract, or in the laboratory. How then do these strains control their metabolism so that they use nutrients efficiently? We have identified a genetic locus, the zor-orz locus, within the pathogen E. coli O157:H7 EDL933. The zor-orz locus is comprised of two zor genes, which encode highly hydrophobic, 29 amino acid proteins, and two orz genes, which encode antisense, small RNAs that repress zor gene expression. Deletion of the entire four-gene locus in EDL933 leads to altered levels of many metabolites and global changes in gene expression. Our data also suggests that zor gene expression is regulated by the nutritional status of cell. Combining these observations, we hypothesize that the zor-orz locus is involved in the control of cellular metabolism. Within this proposal, we will explore this hypothesis by examining how zor gene expression is regulated by the nutrient status of the cell and other elements (Aim 1). We will also explore the function of this locus by determining its effect on gene expression, examining the metabolic differences of these strains, the effects of these deletions on macromolecular synthesis and identifying proteins that interact with the Zors (Aim 2). Combined, these approaches will help unravel the biological role of the zor-orz locus and aid in understanding how organisms control metabolic processes. More broadly, these experiments will provide insights into how bacteria adapt to new niches as well as maintain their foothold on their own environment.
In order for pathogenic bacteria to infect the human intestine, the bacteria must successfully compete for nutrients within the intestine. Our data implicates a role for the zor-orz genes for controlling what nutrients bacteria use and when they use those nutrients during growth. Our work will determine how the zor-orz genes control nutrient consumption and may give insights into how pathogens can infect humans.
|Wen, Jia; Harp, John R; Fozo, Elizabeth M (2017) The 5? UTR of the type I toxin ZorO can both inhibit and enhance translation. Nucleic Acids Res 45:4006-4020|