Uropathogenic Escherichia coli (UPEC), the predominant cause of uncomplicated
urinary tract infection (UTI), utilizes an array of outer membrane
iron receptors to facilitate
siderophore and
heme import from within the
iron-limited urinary tract. While these systems are required for UPEC in vivo fitness and are assumed to be functionally redundant, the relative contributions of specific receptors to pathogenesis are unknown. To delineate the relative roles of distinct UPEC
iron acquisition systems in UTI, isogenic mutants in UPEC strain CFT073 or 536 lacking individual receptors were competed against one another in vivo in a series of
mixed infections. When combinations of up to four mutants were coinoculated using a CBA/J mouse model of ascending UTI, catecholate receptor mutants (ΔfepA, Δiha, and ΔiroN mutants) were equally fit, suggesting redundant function. However, noncatecholate
siderophore receptor mutants, including the ΔiutA
aerobactin receptor mutant and the ΔfyuA
yersiniabactin receptor mutant, were frequently outcompeted by coinoculated mutants, indicating that these systems contribute more significantly to UPEC
iron acquisition in vivo. A tissue-specific preference for
heme acquisition was also observed, as a
heme uptake-deficient Δhma ΔchuA double mutant was outcompeted by
siderophore receptor mutants specifically during kidney colonization. The relative contribution of each receptor to UTI only partially correlated with in vivo levels of receptor gene expression, indicating that other factors likely contributed to the observed fitness differences. Overall, our results suggest that UPEC
iron receptors provide both functional redundancy and niche specificity for this pathogen as it colonizes distinct sites within the urinary tract.