TheEscherichia coliFur pan-regulon has few conserved but many unique regulatory targets

Abstract

While global transcription factors (TFs) have been studied extensively in Escherichia coli model strains, conservation and diversity in TF regulation between strains is still unknown. Here we use a combination of ChIP-exo–to define ferric uptake regulator (Fur) binding sites–and differential gene expression–to define the Fur regulon in nine E. coli strains. We then define a pan-regulon consisting of 469 target genes that includes all Fur target genes in all nine strains. The pan-regulon is then divided into the core regulon (target genes found in all the strains, n = 36), the accessory regulon (target found in two to eight strains, n = 158) and the unique regulon (target genes found in one strain, n = 275). Thus, there is a small set of Fur regulated genes common to all nine strains, but a large number of regulatory targets unique to a particular strain. Many of the unique regulatory targets are genes unique to that strain. This first-established pan-regulon reveals a common core of conserved regulatory targets and significant diversity in transcriptional regulation amongst E. coli strains, reflecting diverse niche specification and strain history.

Iron limitation induces motility in uropathogenic E. coli CFT073 partially through action of LpdA

“…2A ). Furthermore, that same study ( 33 ) showed Fur does not directly bind the fliC promoter, a result corroborated by several other studies ( 25 , 26 ). We also analyzed the upstream intergenic region of fliC using the bioinformatics tool BPROM (Softberry.com), which did not uncover any putative fur boxes.…”

“…This phenotype corresponded with an increase in flagellin transcript, protein, and surface expression of flagella. Knowing that the well-studied Fur regulator was likely not facilitating this regulation in our tested conditions ( 25 , 26 ), we took a forward genetic screening approach to identify the mediator of the iron-restricted enhanced motility phenotype. Through systematic deletion of regulatory genes, we ultimately found that deletion of the gene encoding dihydrolipoyl dehydrogenase, lpdA , led to a loss of iron-mediated motility as well as fitness in vivo .…”

Iron–sulfur cluster assembly scaffold protein IscU is required for activation of ferric uptake regulator (Fur) in Escherichia coli

“…The ferric uptake regulator (Fur) is the founding member of the Fur superfamily that regulates intracellular metal homeostasis in bacteria ( 1 , 2 ). In Escherichia coli , Fur regulates over 158 genes ( 3 , 4 , 5 ) involved in intracellular iron homeostasis, energy metabolism, DNA synthesis, oxidative stress response, and bacterial virulence ( 6 , 7 ). In the past 3 decades, it was postulated that when intracellular free iron content is elevated, Fur binds its corepressor a mononuclear ferrous iron ( 1 , 2 , 8 , 9 ) and regulates the expression of its target genes by binding to a specific DNA sequence known as the Fur-box ( 10 , 11 , 12 ).…”