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

Molecular Microbiology (2009) 71(1), 79-91

Speaker: 謝政原                         Time:13:10~14:00, Mar. 4, 2009

Commentator: 鄧景浩 老師               Place: Room 601

Abstract:

Iron uptake systems are essential for bacterial pathogens to survive in the iron-limiting host environments. The Gram-negative bacteria encode outer membrane receptors which can scavenge haem-bound iron by interacting with an inner membrane protein, TonB. These

proteins share conserved histidine residues and two motifs, the FRAP and NPNL domains. In E.coli pathogens, haem uptake is facilitated by ChuA. It was shown previously that some haem-utilizing strains were chuA-negative, suggesting that an additional haem receptor existed in these strains. It has also been demonstrated that TonB-dependent outer membrane iron receptors are important for host colonization of uropathogenic E.coli (UPEC). A UPEC clinical strain, CFT073, has been shown to possess several iron receptors, but the importance of various host iron sources remains unknown. An iron receptor, Hma, with a putative TonB box at the N-terminal region was then identified in strain CFT073 as an antigenic outer membrane protein that was expressed under iron limitation. Here, the authors further to examined the role of Hma in iron acquisition. In the ascending urinary tract infection model, hma mutant was out-competed by the wild type strian in the kidney and spleen 72 h after inoculating with a 1:1 ratio. Because strain CFT073 encodes another haem receptor, ChuA, the authors used the non-uropathogenic E.coli strain K-12 to identify the specific iron substrate of Hma. The results showed that the wide type, but not the tonB mutant, K-12 strain carring p_nativehma could grow in the presence of haemin in iron-deleted agar. In addition, it was not histidine but tyrosine in Hma that mediated haem uptake. They also found that the hma mutant was better able to compete for chuA mutant in the kidney of co-infection model, although these two receptors showed similar haem-binding affinity. This was because the expression level of chuA was higher than that of hma during iron-limitation. Collectively, the authors have found a novel haem receptor, Hma, that contributes to colonization of UPEC in the kidney and Hma contains a new type of residue, Tyr, for the function of haem uptake.

References:

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2. Hagan, E.C., and Mobley, H.L. (2007) Uropathogenic Escherichia coli outer membrane antigens expressed during urinary tract infection. Infect Immun 75: 3941–3949.