Hagan Erin C, Mobley Harry L T
Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Mol Microbiol. 2009 Jan;71(1):79-91. doi: 10.1111/j.1365-2958.2008.06509.x. Epub 2008 Oct 30.
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, haemacquisition 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 microM). 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.
由特定外膜受体介导的铁摄取对于尿路致病性大肠杆菌（UPEC）在泌尿道的定殖至关重要。然而，特定铁源在体内的作用在很大程度上仍不清楚。在本研究中，我们鉴定出一种79 kDa的血红素受体，血红素获取蛋白Hma，并确定它独立于ChuA发挥作用，介导UPEC菌株CFT073摄取血红素。我们证明hma的表达促进了TonB依赖性血红素利用，并且Hma蛋白以高亲和力（K(d)=8 microM）结合血红素。然而，Hma缺乏已证明可介导其他细菌受体摄取血红素的保守组氨酸残基。相反，我们鉴定出Tyr-126是Hma介导的血红素利用所必需的残基。在UTI的小鼠共感染模型中，同基因hma突变体在感染小鼠的肾脏（P<0.001）和脾脏（P<0.0001）中被野生型CFT073竞争淘汰，表明其表达在这些器官中提供了竞争优势。此外，无法利用血红素的hma chuA双突变体在独立感染期间无法定殖到野生型水平的肾脏中（P = 0.02）。因此，我们证明UPEC在肾脏定殖需要血红素，并且这种铁源的摄取部分由新型受体Hma介导。
