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Tailoring a global iron regulon to a uropathogen

ABSTRACT: Pathogenicity islands and plasmids encode genes for pathogenesis of various Escherichia coli pathotypes.Although there is a basic understanding of the contribution of these virulence factors to disease, less is known about variation in regulatory networks in determining disease phenotypes. Here we dissected aregulatory network directed by the conserved iron homeostasis regulator, Ferric Uptake Regulator (Fur), inuropathogenic E. coli strain CFT073. Comparing anaerobic genome-scale Fur DNA binding, with Fur dependent transcript expression and protein levels of the uropathogen to that of commensal E. coli K-12 strain MG1655, showed that the Fur regulon of the core genome is conserved but also includes genes within the pathogenicity/genetic islands. Unexpectedly, regulons indicative of amino acid limitation and the general stress response were also indirectly activated in the uropathogen fur mutant, suggesting that induction of the Fur regulon increases amino acid demand. Using RpoS levels as a proxy, addition of amino acids mitigated the stress. In addition, iron chelation increased RpoS to the same levels as in the fur mutant. The increased amino acid demand of the fur mutant or iron chelated cells was exacerbated by aerobic conditions, which could be partly explained by the O2-dependent synthesis of the siderophore aerobactin, encoded within a pathogenicity island. Taken together, this data suggest in the iron-poor environment of the urinary tract, amino acid availability could play a role in the proliferation of this uropathogen, particularly if there is sufficient O2 to produce aerobactin.

ORGANISM(S): Escherichia coli CFT073

PROVIDER: GSE145424 | GEO | 2020/03/10

REPOSITORIES: GEO

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Tailoring a global iron regulon to a uropathogen

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