Stojiljkovic I, Larson J, Hwa V, Anic S, So M
Department of Molecular Microbiology and Immunology, Oregon Health Sciences University, Portland, 97201, USA.
J Bacteriol. 1996 Aug;178(15):4670-8. doi: 10.1128/jb.178.15.4670-4678.1996.
We have recently cloned and characterized the hemoglobin receptor gene from Neisseria meningitidis serogroup C. N. meningitidis cells expressing HmbR protein were able to bind biotinylated hemoglobin, and the binding was specifically inhibited by unlabeled hemoglobin and not heme. The HmbR-mediated hemoglobin binding activity of N. meningitidis cells was shown to be iron regulated. The presence of hemoglobin but not heme in the growth medium stimulated HmbR-mediated hemoglobin binding activity. The efficiency of utilization of different hemoglobins by the HmbR-expressing N. meningitidis cells was shown to be species specific; human hemoglobin was the best source of iron, followed by horse, rat, turkey, dog, mouse, and sheep hemoglobins, The phenotypic characterization of HmbR mutants of some clinical strains of N. meningitidis suggested the existence of two unrelated hemoglobin receptors. The HmbR-unrelated hemoglobin receptor was shown to be identical to Hpu, the hemoglobin-haptoglobin receptor of N. meningitidis. The Hpu-dependent hemoglobin utilization system was not able to distinguish between different sources of hemoglobin; all animal hemoglobins were utilized equally well. HmbR-like genes are also present in N. meningitidis serogroups A and B, Neisseria gonorrhoeae MS11 and FA19, Neisseria perflava, and Neisseria polysaccharea. The hemoglobin receptor genes from N. meningitidis serogroups A and B and N. gonorrhoeae MS11 were cloned, and their nucleotide sequences were determined. The nucleotide sequence identity ranged between 86.5% (for N. meningitidis serogroup B hmbR and MS11 hmbR) and 93.4% (for N. meningitidis serogroup B hmbR and N. meningitidis serogroup C hmbR). The deduced amino acid sequences of these neisserial hemoglobin receptors were also highly related, with overall 84.7% conserved amino acid residues. A stop codon was found in the hmbR gene of N. gonorrhoeae MS11. This strain was still able to use hemoglobin and hemoglobin-haptoglobin complexes as iron sources, indicating that some gonococci may express only the HmbR-independent hemoglobin utilization system.
我们最近克隆并鉴定了脑膜炎奈瑟菌C群的血红蛋白受体基因。表达HmbR蛋白的脑膜炎奈瑟菌细胞能够结合生物素化的血红蛋白，且这种结合能被未标记的血红蛋白特异性抑制，而不能被血红素抑制。脑膜炎奈瑟菌细胞的HmbR介导的血红蛋白结合活性显示受铁调节。生长培养基中存在血红蛋白而非血红素会刺激HmbR介导的血红蛋白结合活性。表达HmbR的脑膜炎奈瑟菌细胞对不同血红蛋白的利用效率显示具有物种特异性；人血红蛋白是最佳铁源，其次是马、大鼠、火鸡、狗、小鼠和羊的血红蛋白。一些脑膜炎奈瑟菌临床菌株的HmbR突变体的表型特征表明存在两种不相关的血红蛋白受体。已证明与HmbR不相关的血红蛋白受体与脑膜炎奈瑟菌的血红蛋白-触珠蛋白受体Hpu相同。依赖Hpu的血红蛋白利用系统无法区分不同来源的血红蛋白；所有动物血红蛋白的利用效果相同。A群和B群脑膜炎奈瑟菌、淋病奈瑟菌MS11和FA19、微黄奈瑟菌以及多糖奈瑟菌中也存在HmbR样基因。克隆了A群和B群脑膜炎奈瑟菌以及淋病奈瑟菌MS11的血红蛋白受体基因，并测定了它们的核苷酸序列。核苷酸序列同一性在86.5%（B群脑膜炎奈瑟菌hmbR和MS11 hmbR）至93.4%（B群脑膜炎奈瑟菌hmbR和C群脑膜炎奈瑟菌hmbR）之间。这些奈瑟菌血红蛋白受体的推导氨基酸序列也高度相关，总体保守氨基酸残基为84.7%。在淋病奈瑟菌MS11的hmbR基因中发现了一个终止密码子。该菌株仍能够利用血红蛋白和血红蛋白-触珠蛋白复合物作为铁源，这表明一些淋球菌可能仅表达不依赖HmbR的血红蛋白利用系统。
