Simpson Waltena, Olczak Teresa, Genco Caroline A
Department of Medicine, Section of Infectious Diseases, Boston University School of Medicine, Boston, MA 02118, USA.
Acta Biochim Pol. 2004;51(1):253-62.
We have previously reported on the identification and characterization of the Porphyromonas gingivalis A7436 strain outer membrane receptor HmuR, which is involved in the acquisition of hemin and hemoglobin. We demonstrated that HmuR interacts with the lysine- (Kgp) and arginine- (HRgpA) specific proteases (gingipains) and that Kgp and HRgpA can bind and degrade hemoglobin. Here, we report on the physiological significance of the HmuR-Kgp complex in heme utilization in P. gingivalis through the construction and characterization of a defined kgp mutant and a hmuR kgp double mutant in P. gingivalis A7436. The P. gingivalis kgp mutant exhibited a decreased ability to bind both hemin and hemoglobin. Growth of this strain with hemoglobin was delayed and its ability to utilize hemin as a sole iron source was diminished as compared to the wild type strain. Inactivation of both the hmuR and kgp genes resulted in further decreased ability of P. gingivalis to bind hemoglobin and hemin, as well as diminished ability to utilize either hemin or hemoglobin as a sole iron source. Collectively, these in vivo results further confirmed that both HmuR and Kgp are involved in the utilization of hemin and hemoglobin in P. gingivalis A7436.
我们之前曾报道过牙龈卟啉单胞菌A7436菌株外膜受体HmuR的鉴定与特性，该受体参与血红素和血红蛋白的摄取。我们证明HmuR与赖氨酸特异性蛋白酶（Kgp）和精氨酸特异性蛋白酶（HRgpA）相互作用，且Kgp和HRgpA能够结合并降解血红蛋白。在此，我们通过构建和鉴定牙龈卟啉单胞菌A7436中特定的kgp突变体和hmuR kgp双突变体，报告了HmuR-Kgp复合物在牙龈卟啉单胞菌血红素利用中的生理意义。牙龈卟啉单胞菌kgp突变体结合血红素和血红蛋白的能力均下降。与野生型菌株相比，该菌株利用血红蛋白生长延迟，且其将血红素作为唯一铁源的利用能力降低。hmuR和kgp基因的失活导致牙龈卟啉单胞菌结合血红蛋白和血红素的能力进一步下降，以及将血红素或血红蛋白作为唯一铁源的利用能力降低。总体而言，这些体内实验结果进一步证实HmuR和Kgp均参与牙龈卟啉单胞菌A7436中血红素和血红蛋白的利用。
