Haem acquisition is facilitated by a novel receptor Hma and required by uropathogenic Escherichia coli for kidney infection |
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Authors: | Erin C Hagan Harry L T Mobley |
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Institution: | Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109, USA. |
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Abstract: | 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, h ae m a cquisition 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 ( K d = 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. |
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