Haem acquisition is facilitated by a novel receptor Hma and required by uropathogenic Escherichia coli for kidney infection

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Abstract
Summary: Iron acquisition, mediated by specific outer membrane receptors, is critical for colonization of the urinary tract by uropathogenic Escherichia coli (UPEC). The role of specific iron sources in vivo, however, remains largely unknown. In this study, we identified a 79 kDa haem receptor, haem acquisition protein Hma, and established that it functions independently of ChuA to mediate haemin uptake by UPEC strain CFT073. We demonstrated that expression of hma promotes TonB‐dependent haemin utilization and the Hma protein binds haemin with high affinity (Kd = 8 μM). Hma, however, lacks conserved His residues shown to mediate haem uptake by other bacterial receptors. In contrast, we identified Tyr‐126 as a residue necessary for Hma‐mediated haemin utilization. In a murine co‐infection model of UTI, an isogenic hma mutant was out‐competed by wild‐type CFT073 in the kidneys (P < 0.001) and spleens (P < 0.0001) of infected mice, indicating its expression provided a competitive advantage in these organs. Furthermore, a hma chuA double mutant, which is unable to utilize haemin, was unable to colonize the kidneys to wild‐type levels during independent infection (P = 0.02). Thus, we demonstrate that UPEC requires haem for kidney colonization and that uptake of this iron source is mediated, in part, by the novel receptor, Hma.