Urinary tract infections impose substantial health burdens on women worldwide.
Urinary tract infections often incur a high risk of recurrence and antibiotic resistance, and uropathogenic E. coli accounts for approximately 80% of clinically acquired cases. The diagnosis of, treatment of, and
drug development for
urinary tract infections remain substantial challenges due to the complex pathogenesis of this condition. The clinically isolated UPEC 83972 strain was found to produce four
siderophores:
yersiniabactin,
aerobactin,
salmochelin, and
enterobactin. The biosyntheses of some of these
siderophores implies that the virulence of UPEC is mediated via the targeting of primary metabolism. However, the differential modulatory roles of
siderophore biosyntheses on the differential metabolomes of UPEC and non-UPEC strains remain incompletely understood. In the present study, we sought to investigate how the differential metabolomes can be used to distinguish UPEC from non-UPEC strains and to determine the associated regulatory roles of
siderophore biosynthesis. Our results are the first to demonstrate that the identified differential metabolomes strongly differentiated UPEC from non-UPEC strains. Furthermore, we performed metabolome assays of mutants with different patterns of
siderophore deletions; the data revealed that the mutations of all four
siderophores exerted a stronger modulatory role on the differential metabolomes of the UPEC and non-UPEC strains relative to the mutation of any single
siderophore and that this modulatory role primarily involved
amino acid metabolism, oxidative phosphorylation in the carbon fixation pathway, and
purine and
pyrimidine metabolism. Surprisingly, the modulatory roles were strongly dependent on the type and number of mutated
siderophores. Taken together, these results demonstrated that
siderophore biosynthesis coordinately modulated the differential metabolomes and thus may indicate novel targets for virulence-based diagnosis,
therapeutics, and
drug development related to
urinary tract infections.