Urinary tract infections (UTI) are common and represent a substantial economic and public health burden. Roughly 80% of these
infections are caused by a heterogeneous group of uropathogenic Escherichia coli (UPEC) strains.
Antibiotics are standard
therapy for UTI, but a rise in antibiotic resistance has complicated treatment, making the development of a UTI
vaccine more urgent.
Iron receptors are a promising new class of
vaccine targets for UTI, as UPEC require
iron to colonize the
iron-limited host urinary tract and genes encoding
iron acquisition systems are highly expressed during
infection. Previously, three of six UPEC
siderophore and
heme receptors were identified as
vaccine candidates by intranasal immunization in a murine model of ascending UTI. To complete the assessment of
iron receptors as
vaccine candidates, an additional six UPEC
iron receptors were evaluated. Of the six
vaccine candidates tested in this study (FyuA, FitA,
IroN, the gene product of the CFT073 locus c0294, and two truncated derivatives of ChuA), only FyuA provided significant protection (P = 0.0018) against UPEC colonization. Intranasal immunization induced a robust and long-lived humoral immune response. In addition, the levels of FyuA-specific serum
IgG correlated with bacterial loads in the kidneys [Spearman's rank correlation coefficient ρ(14) = -0.72, P = 0.0018], providing a surrogate of protection. FyuA is the fourth UPEC
iron receptor to be identified from our screens, in addition to IutA, Hma, and IreA, which were previously demonstrated to elicit protection against UPEC challenge. Together, these
iron receptor
antigens will facilitate the development of a broadly protective, multivalent UTI
vaccine to effectively target diverse strains of UPEC.