ROLES OF PORPHYRINS AND HOST IRON TRANSPORT PROTEINS IN REGULATION OF GROWTH OF PORPHYROMONAS-GINGIVALIS W50
ROLES OF PORPHYRINS AND HOST IRON TRANSPORT PROTEINS IN REGULATION OF GROWTH OF PORPHYROMONAS-GINGIVALIS W50
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DOI：
10.1128/jb.173.22.7330-7339.1991
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发表时间：
1991-11-01
影响因子：
3.2
通讯作者：
HOLT, SC
中科院分区：
文献类型：
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作者：
BRAMANTI, TE;HOLT, SC
牙龈卟啉单胞菌(Bacteroids Gigivalis)在体外的生长和毒力需要以氯化血红素形式存在的铁，但卟啉环结构、与卟啉相关的铁、宿主血球蛋白和宿主抑铁蛋白对其存活的贡献尚不清楚。因此，我们研究了不同的卟啉、宿主铁转运蛋白和无机铁源对牙龈假单胞菌W50生长的影响，以描述用于细胞代谢的各种类型的铁分子。细胞膜相关的氯化血红素和铁的储存有助于牙龈假单胞菌在无氯化血红素培养中的生长，而这些内源储备的耗尽需要8次连续转移到无氯化血红素的培养基中，以完全抑制生长。牙龈假单胞菌的生长与血红素(HGB)、高铁血红蛋白、肌红蛋白、饱和血白蛋白、乳过氧化物酶、细胞色素c和过氧化氢酶的7.7mU-M当量相当。在结合珠蛋白-HGB和血凝素-氯化血红素复合体的存在下，记录到了不受限制的生长，这表明这些宿主防御蛋白不会隔离牙龈假单胞菌的HGB和氯化血红素。铁络合剂2，2‘-联吡啶对氯化血红素相关的铁具有功能性螯合作用，导致在浓度为1至25-mU-M2，2，2’-联吡啶的氯化血红素限制培养中，生长受到剂量依赖的抑制。在没有外源铁源的情况下，原卟啉IX不支持牙龈假单胞菌的生长。这些发现表明，氯化血红素分子中的铁原子是生长的关键成分，四吡咯卟啉环结构可能是将铁输送到牙龈假单胞菌细胞内的重要载体。牙龈假单胞菌对卟啉没有严格的要求，因为生长是在非氯化血红素铁源下进行的，包括高浓度(200-mU-M)的铁、铁和氮无机铁，而且牙龈假单胞菌在宿主转铁蛋白、乳铁蛋白和血清白蛋白的存在下表现出不受限制的生长。牙龈假单胞菌利用铁底物的多样性，以及其在牙周袋中可能遇到的宿主抑铁蛋白不影响其生长的观察，可能解释了为什么牙龈假单胞菌在牙周疾病过程中是如此强大的病原体。
Porphyromonas gingivalis (Bacteroides gingivalis) requires iron in the form of hemin for growth and virulence in vitro, but the contributions of the porphyrin ring structure, porphyrin-associated iron, host heminsequestering molecules, and host iron-withholding proteins to its survival are unknown. Therefore, the effects of various porphyrins, host iron transport proteins, and inorganic iron sources on the growth of P. gingivalis W50 were examined to delineate the various types of iron molecules used for cellular metabolism. Cell envelope-associated hemin and iron stores contributed to the growth of P. gingivalis in hemin-free culture, and depletion of these endogenous reserves required eight serial transfers into hemin-free medium for total suppression of growth. Comparable growth of P. gingivalis was observed with 7.7-mu-M equivalents of hemin as hemoglobin (HGB), methemoglobin, myoglobin, hemin-saturated serum albumin, lactoperoxidase, cytochrome c, and catalase. Unrestricted growth was recorded in the presence of haptoglobin-HGB and hemopexin-hemin complexes, indicating that these host defense proteins do not sequester HGB and hemin from P. gingivalis. The iron chelator 2,2'-bipyridyl functionally chelated hemin-associated iron, resulting in dose-dependent inhibition of growth in hemin-restricted cultures at 1 to 25-mu-M 2,2'-bipyridyl concentrations. In the absence of an exogenous iron source, protoporphyrin IX did not support P. gingivalis growth. These findings suggest that the iron atom in the hemin molecule is the critical constituent for growth and that the tetrapyrrole porphyrin ring structure may represent an important vehicle for delivery of iron into the P. gingivalis cell. P. gingivalis does not have a strict requirement for porphyrins, since growth occurred with nonhemin iron sources, including high concentrations (200-mu-M) of ferric, ferrous, and nitrogenous inorganic iron, and P. gingivalis exhibited unrestricted growth in the presence of host transferrin, lactoferrin, and serum albumin. The diversity of iron substrates utilized by P. gingivalis and the observation that growth was not affected by the bacteriostatic effects of host iron-withholding proteins, which it may encounter in the periodontal pocket, may explain why P. gingivalis is such a formidable pathogen in the periodontal disease process.