Uropathogenic Escherichia coli wield enterobactin-derived catabolites as siderophores

Zongsen Zou, John I. Robinson, Lindsey K. Steinberg, Jeffrey P. Henderson

Research output: Contribution to journalArticlepeer-review


Uropathogenic Escherichia coli (UPEC) secrete multiple siderophore types to scavenge extracellular iron(III) ions during clinical urinary tract infections, despite the metabolic costs of biosynthesis. Here, we find the siderophore enterobactin (Ent) and its related products to be prominent components of the iron-responsive extracellular metabolome of a model UPEC strain. Using defined Ent biosynthesis and import mutants, we identify lower molecular weight dimeric exometabolites as products of incomplete siderophore catabolism, rather than prematurely released biosynthetic intermediates. In E. coli, iron acquisition from iron(III)–Ent complexes requires intracellular esterases that hydrolyze the siderophore. Although UPEC are equipped to consume the products of completely hydrolyzed Ent, we find that Ent and its derivatives may be incompletely hydrolyzed to yield products with retained siderophore activity. These results are consistent with catabolic inefficiency as means to obtain more than one iron ion per siderophore molecule. This is compatible with an evolved UPEC strategy to maximize the nutritional returns from metabolic investments in siderophore biosynthesis.

Original languageEnglish
Article number105554
JournalJournal of Biological Chemistry
Issue number1
StatePublished - Jan 2024


  • enterobactin
  • Escherichia coli
  • exometabolome
  • Gram-negative bacteria
  • iron
  • metabolomics
  • siderophore


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