Hemin-dependent modulation of the lipid a structure of Porphyromonas gingivalis lipopolysaccharide
Hemin-dependent modulation of the lipid a structure of Porphyromonas gingivalis lipopolysaccharide
复制标题
DOI：
10.1128/iai.01924-05
复制
发表时间：
2006-08-01
影响因子：
3.1
通讯作者：
Darveau, Richard P.
中科院分区：
文献类型：
--
作者：
Al-Qutub, Montaser N.;Braham, Pamela H.;Darveau, Richard P.
牙龈卟啉单胞菌是一种与成人型牙周炎密切相关的牙周病原菌。牙周病原菌的毒力特征和宿主相关因素被认为是牙周炎的原因。牙龈卟啉单胞菌脂多糖（LPS）显示出显著量的脂质A结构异质性，含有五酰化和四酰化脂质A结构。然而，关于牙龈卟啉单胞菌的脂质A结构含量是如何调节的知之甚少。脂质A含量的改变可促进牙龈卟啉单胞菌调节宿主对该细菌的先天反应的能力。在这份报告中，它表明，氯化血红素在生长培养基中的浓度显着调节牙龈卟啉单胞菌的脂多糖脂质A的结构含量。氯化血红素是牙龈颈液的关键微环境成分，据信其根据血管溃疡的状态而变化。在低浓度的氯化血红素，一个主要的五酰化脂质A结构被发现，而在高浓度的氯化血红素，多个四和五酰化脂质A结构观察。氯化血红素浓度，而不是铁的收购，负责脂质A结构含量的改变。脂质A结构含量的修改是独立的LPS提取程序，并发生在各种实验室菌株以及新鲜获得的临床分离株。已知的氯化血红素结合蛋白Kgp和HmuR有助于脂质A的调制传感机制。据我们所知，这是第一份报告，氯化血红素，牙龈卟啉单胞菌的临床相关微环境成分，可以调节在细菌中发现的脂质A结构。由于四酰化和五酰化牙龈卟啉单胞菌脂质A结构对Toll样受体4活化具有相反的作用，脂质A结构含量的改变可能对宿主对该细菌的反应具有显著影响。
Porphyromonas gingivalis is a periopathogen strongly associated with the development of adult-type periodontitis. Both the virulence characteristics of periopathogens and host-related factors are believed to contribute to periodontitis. P. gingivalis lipopolysaccharide (LPS) displays a significant amount of lipid A structural heterogeneity, containing both penta- and tetra-acylated lipid A structures. However, little is known concerning how the lipid A structural content of P. gingivalis is regulated. Alterations in the lipid A content may facilitate the ability of P. gingivalis to modulate the innate host response to this bacterium. In this report, it is shown that the concentration of hemin in the growth medium significantly modulates the lipopolysaccharide lipid A structural content of P. gingivalis. Hemin is a key microenvironmental component of gingival cervicular fluid which is believed to vary depending upon the state of vascular ulceration. At low hemin concentrations, one major penta-acylated lipid A structure was found, whereas at high concentrations of hemin, multiple tetra and penta-acylated lipid A structures were observed. Hemin concentrations, not iron acquisition, were responsible for the alterations in the lipid A structural content. The modifications of the lipid A structural content were independent of the LPS extraction procedure and occurred in a variety of laboratory strains as well as a freshly obtained clinical isolate. The known hemin binding proteins Kgp and HmuR contributed to the lipid A modulation sensing mechanism. To the best of our knowledge, this is the first report that hemin, a clinically relevant microenvironmental component for P. gingivalis, can modulate the lipid A structure found in a bacterium. Since tetra- and penta-acylated P. gingivalis lipid A structures have opposing effects on Toll-like receptor 4 activation, the alteration of the lipid A structural content may have significant effects on the host response to this bacterium.